Angiotenin II antagonizing heterocyclic derivatives

ABSTRACT

The invention relates to compounds of the formula ##STR1## wherein ##STR2## represents a condensed or uncondensed imidazolyl ring and the rest of the variables are as defined in the specification. They are angiotensin II antagonists useful for treating hypertension, etc..

This application is a continuation-in-part of U.S. application Ser. No.07/748,954, filed Aug. 23, 1991.

The present invention relates to novel heterocyclic derivatives and apharmaceutically acceptable salt thereof. More particularly, it relatesto novel imidazole derivatives and a pharmaceutically acceptable saltthereof which have pharmacological activities such as angiotensin IIantagonism and the like, to process for preparation thereof, to apharmaceutical composition comprising the same and to a use of the sameas a medicament.

Accordingly, one object of the present invention is to provide novelimidazole derivatives and a pharmaceutically acceptable salt thereof,which are useful as a potent and selective antagonist of angiotensin IIreceptor.

Another object of the present invention is to provide process forpreparation of said imidazole derivatives or a salt thereof.

A further object of the present invention is to provide a pharmaceuticalcomposition comprising, as an active ingredient, said imidazolederivatives or a pharmaceutically acceptable salt thereof.

Still further object of the present invention is to provide a use ofsaid imidazole derivatives or a pharmaceutically acceptable salt thereofas a medicament such as angiotensin II antagonist useful for treating orpreventing angiotensin II mediated diseases, for example, hypertension(e.g. essential hypertension, renal hypertension, etc.), heart failure,and the like in human being or animals.

The imidazole derivatives of the present invention are novel and can berepresented by the formula (I) : ##STR3## wherein R¹ is hydrogen,halogen, nitro, lower alkyl, lower alkoxy, amino or acylamino,

R², R³ and R⁴ are each hydrogen, halogen, nitro, cyano, lower alkyl,lower alkenyl, lower alkylthio, more or di or trihalo(lower)alkyl,oxo(lower)alkyl, hydroxy(lower)alkyl or optionally esterified carboxy;or

R² and R³ are linked together to form 1,3-butadienylene,

R⁵ is hydrogen or imino-protective group,

A is lower alkylene,

Q is CH or N,

X is N or CH,

Y is NH, O or S, and ##STR4## is condensed or uncondensed imidazolylwhich may have suitable substituent(s).

According to the present invention, the object compound (I) can beprepared by the following processes. ##STR5## Wherein R¹, R², R³, R⁴,R⁵, A, Q, X, Y and ##STR6## each as defined above, R_(a) ⁴ isoxo(lower)alkyl or halogen,

R_(b) ⁴ is hydroxy(lower)alkyl or hydrogen,

R_(a) ⁵ is imino-protective group, and

R⁶ is acid residue.

Suitable salts of the compound (I) are conventional non-toxic,pharmaceutically acceptable salt and may include a salt with a base oran acid addition salt such as a salt with an inorganic base, forexample, an alkali metal salt (e.g. sodium salt, potassium salt, cesiumsalt, etc.), an alkaline earth metal salt (e.g. calcium salt, magnesiumsalt, etc.), an ammonium salt; a salt with an organic base, for example,an organic amine salt (e.g. triethylamine salt, pyridine salt, picolinesalt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt,N,N'-dibenzylethylenediamine salt, etc.), etc.; an inorganic acidaddition salt (e.g. hydrochloride, hydrobromide, sulfate, phosphate,etc.); an organic carboxylic or sulfonic acid addition salt (e.g.formate, acetate, trifluoroacetate, maleate, tartrate, methanesulfonate,benzenesulfonate, p-toluenesulfonate, etc.); a salt with a basic oracidic amino acid (e.g. arginine, aspartic acid, glutamic acid, etc.);and the like, and the preferable example thereof is an acid additionsalt.

In the above and subsequent descriptions of the present specification,suitable examples and illustrations of the various definitions which thepresent invention include within the scope thereof are explained indetail as follows.

The term "lower" is intended to mean 1 to 6 carbon atoms, preferably 1to 4 carbon atoms, unless otherwise indicated.

Suitable "lower alkyl" and lower alkyl group in the term "loweralkylthio" may include straight or branched one, having 1 to 6 carbonatom(s), such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl,pentyl, hexyl, preferably one having 1 to 5 carbon atoms, and the like.

Suitable "lower alkenyl" may include vinyl, 1-propenyl, allyl,1-butenyl, 2-butenyl, 2-pentenyl, and the like, preferably one having 2to 4 carbon atoms, in which the most preferred one is vinyl.

Suitable "lower alkylene" is one having 1 to 6 carbon atom(s) and mayinclude methylene, ethylene, trimethylene, propylene, tetramethylene,methyltrimethylene, dimethylethylene, hexamethylene, and the like, inwhich the preferred one is methylene.

Suitable "halogen" means fluoro, chloro, bromo and iodo.

Suitable "lower alkoxy" may include straight or branched one such asmethoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy,pentyloxy, hexyloxy or the like, in which the preferable one is C₁ -C₄alkoxy.

Suitable acyl group in the term "acylamino" may include carbamoyl,thiocarbamoyl, sulfamoyl, aliphatic acyl, aromatic acyl, heterocyclicacyl, in which the preferable one is aliphatic acyl such as loweralkanoyl (e.g. formyl, acetyl, propionyl, butyryl, hexanoyl, etc.).

Suitable "mono or di or trihalo(lower)alkyl" may include chloromethyl,fluoromethyl, difluoromethyl, dichloromethyl, trifluoromethyl,trifluoromethylpropyl, and the like.

Suitable "hydroxy(lower)alkyl" may include hydroxymethyl, hydroxyetyl,and the like.

Suitable "oxo(lower)alkyl" may include formyl, formylmethyl,formylethyl, and the like.

Suitable "esterified carboxy" may include lower alkoxycarbonyl (e.g.methoxycarbonyl, ethoxycarbonyl, etc.), and the like.

Suitable "imino-protective group" may include conventional one, and thepreferable example thereof is ar(lower)alkyl such as mono-(or di- ortri-)phenyl(lower)alkyl (e.g. benzyl, benzhydryl, trityl, etc.), acylsuch as lower alkoxycarbonyl (e.g. tert-butoxycarbonyl, etc.), loweralkanesulfonyl (e.g. mesyl, etc.), arenesulfonyl (e.g. tosyl, etc.), andthe like, in which the most preferred one is trityl.

The term "condensed on uncondensed imidazolyl" means 1H-imidazol-1-ylwhich may be condensed with aromatic or heterocyclic ring, and suchgroup may include benzene, naphthalene, 5 or 6- membered aromaticheteromonocyclic group such as 5 or 6- membered aromaticheteromonocyclic group containing 1 to 2- nitrogen atom(s) (e.g.pyrrole, imidazole, pyrazole, pyridine, pyrimidine, etc.), 5 or6-membered aromatic heteromonocyclic group containing 1 oxygen atom(e.g. furan, etc.), 5 or 6- membered aromatic heteromonocyclic groupcontaining 1 sulfur atom (e.g. thiophene, etc.), and the like.

Suitable substituent in the term "condensed or uncondensed imidazolylwhich may have suitable substituent(s)" is conventional one used in apharmaceutical field and may include lower alkyl, halogen, lower alkoxy,hydroxy(lower)alkyl as mentioned above, respectively; optionallyesterified carboxy such as carboxy, lower alkoxycarbonyl (e.g.ethoxycarbonyl, etc.); and the like.

Particularly, the preferred embodiment of ##STR7## is as follows.2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-ethyl-3H-imidazo[4,5-b]pyridin-3-yl,2-propyl-3H-imidazo[4,5-b]pyridin-3-yl, 2-butyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.); lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yle.g. 2-ethyl-7-methyl-3H-imidazo[4,5-b]pyridin-3-yl,-methyl-2-propyl-3H-imidazo[4,5-b]pyridin-3-yl,-butyl-7-methyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.),2,5,7-tri(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl,5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.);5-halo-2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-butyl-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 5-loweralkoxy-2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.-butyl-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl, etc.), -loweralkoxycarbonyl-2-lower alkyl-1H-benzimidazol-1-yl (e.g.2-butyl-6-ethoxycarbonyl-1H-benzimidazol-1-yl, etc.), 2-loweralkyl-3H-imidazo[4,5-d]pyrimidin-3-yl (e.g.-butyl-3H-imidazo[4,5-d]pyrimidin-3-yl, etc.), 2-loweralkyl-1H-thieno[3,4-d] imidazol-1-yl (e.g.2-butyl-1H-thieno[3,4-d]imidazol-1-yl, etc.), 2-loweralkyl-4-halo-5-hydroxy(lower)alkyl-1H-imidazol-1-yl (e.g.2-butyl-4-chloro-5-hydroxymethyl-1H-imidazol-1-yl, etc.) and morepreferably 2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl,2,7-di(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl and2,5,7-tri(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl.

Suitable "acid residue" may include halogen (e.g. fluoro, chloro, bromo,iodo),acyloxy (e.g. acetoxy, tosyloxy, mesyloxy, etc.) and the like.

The preferred embodiment of the heterocyclic derivatives (I) of thepresent invention can be represented by the following chemical formula:##STR8## wherein R^(a) is lower alkyl,

R^(b) is hydrogen or lower alkyl,

A is lower alkylene, and

R², R³ and R⁴ are each hydrogen, halogen or nitro; or

R² and R³ are linked together to form 1,3-butadienylene,

in which lower alkyl, lower alkylene and halogen are each the same asthose mentioned above.

Also, the preferred embodiment of the compound (I) can be represented bythe following formula. ##STR9## wherein R^(a) is lower alkyl,

R^(b) is hydrogen or lower alkyl,

R¹ is hydrogen, halogen, nitro, lower alkoxy, amino or acylamino,

A is lower alkylene,

Q is CH or N, and

R², R³ and R⁴ are each hydrogen, halogen or nitro; or

R² and R³ are linked together to form 1,3-butadienylene,

in which lower alkyl, halogen, lower alkoxy, acylamino and loweralkylene are each the same as those mentioned above.

Also, the preferred embodiment of the compound (I) can be represented bythe following formula. ##STR10## wherein R¹ is hydrogen, halogen, nitro,lower alkyl, lower alkoxy, amino or acylamino,

R², R³ and R⁴ are each hydrogen, halogen, nitro, cyano, lower alkyl orlower alkenyl; or

R² and R³ are linked together to form 1,3-butadienylene,

A is lower alkylene,

Q is CH or N, and ##STR11## is condensed or uncondensed imidazolyl whichmay have suitable substituent(s),

in which each of these definitions is the same as those mentioned above,and more preferred example of ##STR12## may be: 2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-propyl-3H-imidazo[4,5-b]pyridin-3-yl,2-butyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.);2,7-di(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.7-methyl-2-propyl-3H-imidazo[4,5-b]pyridin-3-yl,2-butyl-7-methyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 5-halo-2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-butyl-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 5-loweralkyl-2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-butyl-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 6-loweralkoxycarbonyl-2-lower alkyl-1H-benzimidazol-1-yl (e.g.2-butyl-6-ethoxycarbonyl-1H-benzimidazol-1-yl, etc.), 2-loweralkyl-3H-imidazo[4,5-d]pyrimidin-3-yl (e.g.2-butyl-3H-imidazo[4,5-d]pyrimidin-3-yl, etc.), 2-loweralkyl-1H-thieno[3,4-d]imidazol-1-yl (e.g. 2-butyl-1H-thieno[3,4-d]imidazol-1-yl, etc.), 2-loweralkyl-4-halo-5-hydroxy(lower)alkyl-1H-imidazol-1-yl (e.g.2-butyl-4-chloro-5-hydroxymethyl-1H-imidazol-1-yl, etc.); and morepreferred example of its substituent may be: lower alkyl, halogen, loweralkoxy, optionally esterified carboxy as explained above, respectively.

Also, the preferred embodiment of the compound (I) can be represented bythe following formula. ##STR13## wherein R¹ is hydrogen, halogen, nitro,lower alkyl, lower alkoxy, amino or acylamino,

R², R³ and R⁴ are each hydrogen, halogen, nitro, cyano, lower alkyl,lower alkenyl, lower alkylthio, dihalo(lower)alkyl, oxo(lower)alkyl orhydroxy(lower)alkyl; or

R² and R³ are linked together to form 1,3-butadienylene,

A is lower alkylene,

Q is CH or N, and ##STR14## is condensed or uncondensed imidazolyl whichmay have suitable substituent(s), in which each of these definitions isthe same as those mentioned above, and more preferred example of##STR15## may be: 2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-propyl-3H-imidazo[4,5-b]pyridin-3-yl,2-butyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.);2,7-di(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.7-methyl-2-propyl-3H-imidazo[4,5-b]pyridin-3-yl,2-butyl-7-methyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.),2,5,7-tri(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.);5-halo-2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-butyl-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 5-loweralkoxy-2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-butyl-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 6-loweralkoxycarbonyl-2-lower alkyl-1H-benzimidazol-1-yl (e.g.2-butyl-6-ethoxycarbonyl-1H-benzimidazol-1-yl, etc.), 2-loweralkyl-3H-imidazo[4,5-d]pyrimidin-3-yl (e.g.2-butyl-3H-imidazo[4,5-d]pyrimidin-3-yl, etc.), 2-loweralkyl-1H-thieno[3,4-d]imidazol-1-yl (e.g.2-butyl-1H-thieno[3,4-d]imidazol-1-yl, etc.), 2-loweralkyl-4-halo-5-hydroxy(lower)alkyl-1H-imidazol-1-yl (e.g.2-butyl-4-chloro-5-hydroxymethyl-1H-imidazol-1-yl, etc.); and morepreferred example of its substituent may be: lower alkyl, halogen, loweralkoxy, optionally esterified carboxy as mentioned above, respectively.

Further, the preferred embodiment of the compound (I) can be representedby the following formula. ##STR16## wherein R¹ is hydrogen, halogen,nitro, lower alkyl, lower alkoxy, amino or acylamino,

R², R³ and R⁴ are each hydrogen, halogen, nitro, cyano, lower alkyl,lower alkenyl, lower alkylthio, mono or di or trihalo(lower)alkyl,oxo(lower)alkyl, hydroxy(lower)alkyl or optionally esterified carboxy;or

R² and R³ are linked together to form 5 1,3-butadienylene,

R⁵ is hydrogen or imino-protective group,

A is lower alkylene,

Q is CH or N, and ##STR17## is condensed or uncondensed imidazolyl whichmay have suitable substituent(s),

in which each of these definitions is the same as those mentioned above,and more preferred example of ##STR18## may be: 2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-propyl-3H-imidazo[4,5-b]pyridin-3-yl,2-butyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.);2,7-di(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.7-methyl-2-propyl-3H-imidazo[4,5-b]pyridin-3-yl,2-butyl-7-methyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.),2,5,7-tri(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.);5-halo-2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-butyl-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 5-loweralkoxy-2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-butyl-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 6-loweralkoxycarbonyl-2-lower alkyl-1H-benzimidazol-1-yl (e.g.2-butyl-6-ethoxycarbonyl-1H-benzimidazol-1-yl, etc.), 2-loweralkyl-3H-imidazo[4,5-d]pyrimidin-3-yl (e.g.2-butyl-3H-imidazo[4,5-d]pyrimidin-3-yl, etc.), 2-loweralkyl-1H-thieno[3,4-d]imidazol-1-yl (e.g.2-butyl-1H-thieno[3,4-d]imidazol-1-yl, etc.), 2-loweralkyl-4-halo-5-hydroxy(lower)alkyl-1H-imidazol-1-yl (e.g.2-butyl-4-chloro-5-hydroxymethyl-1H-imidazol- 1-yl, etc.); and morepreferred example of its substituent may be: lower alkyl, halogen, loweralkoxy optionally esterified carboxy as mentioned above, respectively.

Still further, the preferred embodiment of the compound (I) can berepresented by the following formula. ##STR19## wherein R¹ is hydrogen,halogen, nitro, lower alkyl, lower alkoxy, amino or acylamino,

R² and R³ are each hydrogen, halogen, nitro,cyano, lower alkyl or loweralkenyl; or

R² and R³ are linked together to form 1,3-butadienylene,

A is lower alkylene,

Q is CH or N, and ##STR20## is condensed or uncondensed imidazolyl whichmay have suitable substituent(s), in which each of these definitions isthe same as those mentioned above, and more preferred example of##STR21## may be: 2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-propyl-3H-imidazo[4,5-b]pyridin-3-yl,2-butyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.);2,7-di(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.7-methyl-2-propyl-3H-imidazo[4,5-b]pyridin-3-yl,2-butyl-7-methyl-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 5-halo-2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl (e.g.2-butyl-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 5-loweralkyl-2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl e.g.2-butyl-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl, etc.), 6-loweralkoxycarbonyl-2-lower alkyl-1H-benzimidazol-1-yl (e.g.2-butyl-6-ethoxycarbonyl-1H-benzimidazol-1-yl, etc.), 2-loweralkyl-3H-imidazo[4,5-d]pyrimidin-3-yl (e.g.2-butyl-3H-imidazo[4,5-d]pyrimidin-3-yl, etc.), 2-loweralkyl-1H-thieno[3,4-d]imidazol-1-yl (e.g.2-butyl-1H-thieno[3,4-d]imidazol-1-yl, etc.), 2-loweralkyl-4-halo-5-hydroxy(lower)alkyl-1H-imidazol-1-yl (e.g.2-butyl-4-chloro-5-hydroxymethyl-1H-imidazol-1-yl, etc.); and morepreferred example of its substituent may be: lower alkyl, halogen, loweralkoxy, optionally esterified carboxy as mentioned above, respectively.

Particularly, the preferred compound (I) of the present invention isrepresented by the following formula: ##STR22## wherein R², R³ and R⁴are each hydrogen, halogen, nitro, cyano, lower alkyl, lower alkenyl,lower alkylthio, mono or di or trihalo(lower)alkyl, oxo(lower)alkyl,hydroxy(lower)alkyl or optionally esterified carboxy (more preferablycarboxy or lower alkoxycarbonyl); or

R² and R³ are linked together to form 1,3-butadienylene,

Y is NH, O or S and ##STR23## is 2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl,2,7-di(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl,2,5,7-tri(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl, 5-halo-2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl, 5-lower alkoxy-2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl, 6-lower alkoxycarbonyl-2-loweralkyl-1H-benzimidazol-1-yl, 2-loweralkyl-3H-imidazo[4,5-d]pyrimidin-3-yl, 2-loweralkyl-1H-thieno[3,4-d]imidazol-1-yl or 2-loweralkyl-4-halo-5-hydroxy(lower)alkyl-1H-imidazol-1-yl (more preferably,2-lower alkyl-3H-imidazo[4,5-b]pyridin-3-yl,2,7-di(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl or2,5,7-tri(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl),

and further, more preferred embodiment of a group of the formula.##STR24## is represented by the following formula: ##STR25## whereinR_(a) ² is hydrogen, halogen, cyano, lower alkyl or lower alkylthio, andR_(a) ³ is hydrogen, halogen, nitro, lower alkyl, lower alkenyl,trihalo(lower)alkyl, oxo(lower)alkyl, hydroxy(lower)alkyl or loweralkoxycarbonyl; ##STR26## wherein R_(b) ² and R_(b) ³ are each halogen;##STR27## wherein R_(c) ² is hydrogen, halogen or lower alkyl, R_(c) ³is lower alkyl, and R_(c) ⁴ is hydrogen or halogen; ##STR28## whereinR_(d) ² is hydrogne, halogen or lower akyl, and R_(d) ³ is lower alkyl;##STR29## wherein R_(e) ² is hydrogen or halogen; or ##STR30## and themost preferred one is: ##STR31## wherein R_(f) ² and R_(f) ³ are eachhydrogen, lower alkyl or halogen.

The processes for preparing the object compound (I) of the presentinvention are explained in detail in the following.

Process 1

The object compound (I) or a salt thereof can be prepared by subjectingthe compound (II) to the formation reaction of a tetrazole group.

The agent to be used in the present reaction may include conventionalones which is capable of converting a cyano group to a tetrazolyl groupsuch as metal azide, for example, alkali metal azide (e.g., potassiumazide, sodium azide etc.), tri(lower)alkyltin azide (e.g. trimethyltinazide, etc.), triaryltin azide (e.g. triphenyltin azide, etc.), or thelike.

The present reaction is usually carried out in the presence of a basesuch as tri(lower)alkylamine (e.g. triethylamine, etc.), and the like,or 1,3-dimethyl-2-imidazolidinone, and the like.

The present reaction is usually carried out in a solvent such as xylene,dioxane, chloroform, methylene chloride, 1,2-dichloroethane,tetrahydrofuran, pyridine, acetonitrile, dimethylformamide or any othersolvent which does not adversely affect the reaction.

The reaction temperature is not critical and the reaction is usuallycarried out under warming or heating, preferably under heating.

Further, the compound (I) wherein R¹ is amino can be prepared byreducing the corresponding nitro compound in a conventional manner, andthe compound (I) wherein R¹ is acylamino can be prepared by acylatingthe amino compound obtained above in a conventional manner.

And further, the present reaction includes, within its scope, the casethat the dihalo(lower)alkyl group on R², R³ or R⁴ is transformed to theoxo(lower)alkyl group during the reaction or at the post-treating stepof the present process.

Process 2

The object compound (I-b) or a salt thereof can be prepared bysubjecting the compound (I-a) or a salt thereof to reduction.

The reduction may include, for example, chemical reduction with analkali metal borohydride (e.g. sodium borohydride, etc.), and catalyticreduction with palladium catalysts (e.g. palladium on carbon, etc.), andthe like.

This reaction is usually carried out in a conventional solvent whichdoes not adversely influence the reaction such as alcohol [e.g.methanol, ethanol, propanol, etc.], tetrahydrofuran, dioxane, dimethylsulfoxide, N,N-dimethylformamide or a mixture thereof.

The reaction temperature is not critical, and the reaction is usuallycarried out under cooling to heating.

Process 3

The object compound (I) or a salt thereof can be prepared by reactingthe compound (III) or a salt thereof with the compound (IV) or a saltthereof.

The present reaction is usually carried out in the presence of a basesuch as alkyl lithium (e.g. n-butyl lithium, etc.), alkali metal hydride(e.g. sodium hydride, potassium hydride, etc.), di(lower)alkylamine(e.g. diisopropylamine, etc.), tri(lower)alkylamine (e.g.trimethylamine, triethylamine, etc.), pyridine or its derivative (e.g.picoline, lutidine, 4-dimethylaminopyridine, etc.), or the like.

The present reaction is usually carried out in a solvent such asdioxane, dimethyl sulfoxide, dimethylformamide, diethylformamide,dimethylacetamide, benzene, tetrahydrofuran, or any other solvent whichdoes not adversely affect the reaction. In case that the base to be usedis liquid, it can also be used as a solvent.

The reaction temperature is not critical and the reaction is usuallycarried out under cooling, at ambient temperature or under heating.

Process 4

The object compound (I-d) or a salt thereof can be prepared bysubjecting the compound (I-c) or a salt thereof to removal reaction ofthe imino-protective group.

Suitable method for this removal may include conventional one which iscapable of removing an imino-protective group on a tetrazolyl group suchas hydrolysis, reduction, or the like. The hydrolysis is preferablycarried out in the presence of the base or an acid.

Suitable base may include, for example, an inorganic base such as alkalimetal hydride (e.g. sodium hydroxide, potassium hydroxide, etc.),alkaline earth metal hydroxide (e.g. magnesium hydroxide, calciumhydroxide, etc.), alkali metal carbonate, (e.g. sodium carbonate,potassium carbonate, etc.), alkaline earth metal carbonate (e.g.magnesium carbonate, calcium carbonate, etc.), alkali metal bicarbonate(e.g. sodium bicarbonate, potassium bicarbonate, etc.), alkali metalacetate [e.g. sodium acetate, potassium acetate, etc.), alkaline earthmetal phosphate (e.g. magnesium phosphate, calcium phosphate, etc.),alkali metal hydrogen phosphate (e.g. disodium hydrogen phosphate,dipotassium hydrogen phosphate, etc.), or the like, and an organic basesuch as trialkylamine (e.g. trimethylamine, triethylamine, etc.),picoline, N-methylpyrrolidine, N-methylmorpholine,1,5-diazabicyclo[4,3,0]non-5-one, 1,4-diazabicyclo[2,2,2]octane,1,5-diazabicyclo[5,4,0]undecene-5 or the like. The hydrolysis using abase is often carried out in water or a hydrophilic organic solvent or amixed solvent thereof.

Suitable acid may include an organic acid (e.g. formic acid acetic acid,propionic acid, etc.) and an inorganic acid (e.g. hydrochloric acid,hydrobromic acid, sulfuric acid, etc.).

The present hydrolysis is usually carried out in an organic solvent,water or a mixed solvent thereof.

The reaction temperature is not critical, and the reaction is usuallycarried out at ambient temperature or under warming or heating.

The starting compounds (II), (III) and (IV) are new and can be preparedby the methods of Preparations mentioned below or a similar mannerthereto or a conventional manner.

The object compound (I) of the present invention can be isolated andpurified in a conventional manner, for example, extractionprecipitation, fractional crystallization, recrystallization,chromtography, and the like.

The object compound (I) thus obtained can be converted to its salt by aconventional method.

The object compound (I) of the present invention exhibits angiotensinantagonism such as vasodilating activity and is useful as an angiotensinII antagonist and effective to various angiotensin II mediated diseasessuch as hypertension (e.g. essential hypertension, renal hypertension,etc.), heart failure, and the like.

Further, it is expected that the object compounds of the presentinvention are useful as therapeutical and/or preventive agents forcardiopathy (e.g. angina pectoris, arrhythmia, myocardial infarction,etc.), hyperaldosteronism, cerebral vascular diseases, senile dementia,ophthalimic diseases (e.g. glaucoma, etc.), and the like; and diagnosticagents to test the renin angiotensin system.

In order to illustrate the usefulness of the object compounds (I),pharmacological activity of representative compounds of the presentinvention is shown below.

[1] Test Compound

13-[4-[4-Bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine(hereinafter referred to as Compound 1)

[2] Inhibition by the antagonist of contractile response to angiotensinII in excised guinea pig ileum Test Method

Male guinea pigs weighing 300 g to 500 g were sacrificed by decapitationand the ileum were excised. Longitudial strips of the ileum (length: 2cm) were placed in a 25 ml organ bath containing Tyrode's solution ofthe following composition (mM): NaCl, 137; KCl, 2.7; CaCl₂, 1.8; MgCl₂,1.1; NaH₂ PO₄, 0.4; NaHCO₃, 12; Glucose, 5.6.

The bath was maintained at 37° C. and bubbled with 95% O₂ +5% CO₂. Thestrips was stretched with a resting force of 0.5 g, and the isometriccontraction were recorded via force development transducer on anink-writing recorder. The preparation was equilibrated in Tyrode'ssolution mentioned above for 30 minutes, and then exposed to atropine(3.2×10⁻⁷ g/ml) Five minutes later, the response for angiotensin II(1×10⁻⁸ g/ml) was obtained and the preparation was washed a few times.This procedure was repeated twice. After the last response forangiotensin II was obtained (control response), the preparation waswashed, and the response for angiotensin II (10⁻⁸ g/ml) was obtained inthe presence of the test compound The concentration of the test compoundwere 10⁻⁷, 10⁻⁸, 10⁻⁹, 10⁻¹⁰ M. The test compound were added 3 minutesprior to adding angiotensin II. Atropine was also added 5 minutes priorto adding angiotensin II. The inhibition of the test compound forangiotensin II contraction were expressed as a percentage change tocontrol response, and IC₅₀ (M) was calculated.

[3] Test Result

    ______________________________________                                        Compound      IC.sub.50 (M)                                                   ______________________________________                                        1             1.70 × 10.sup.-9                                          ______________________________________                                    

For therapeutic or preventive administration, the object compound (I) ofthe present invention are used in the form of conventionalpharmaceutical preparation which contains said compound as an activeingredient, in admixture with pharmaceutically acceptable carriers suchas an organic or inorganic solid or liquid excipient which is suitablefor oral, parenteral and external administration. The pharmaceuticalprepartion may be in solid form such as tablet, granule, powder,capsule, or liquid form such as solution, suspension, syrup, emulsionlemonade and the like.

If needed, there may be included in the above preparations auxiliarysubstances, stabilizing agents, wetting agents and other commonly usedadditives such as lactose, citric acid, tartaric acid, stearic acid,magnesium stearate, terrra alba, sucrose, corn starch, talc, gelatin,agar, pectin, peanut oil, olive oil, cacao butter, ethylene glycol, andthe like.

While the dosage of the comound (I) may vary from and also depend uonthe age, conditions of the patient, a kind of diseases or conditions, aking of the compound (I) to be applied, etc. In general amounts between0.01 mg of about 500 mg or even more per day may be administered to apatient. An average single dose of about 0.05 mg, 0.1 mg, 0.25 mg, 0.5mg, 1mg, 20 mg, 50 mg, 100 mg of the object comopund (I) of the presentinvention may be used in treating diseases.

The following Preparations and Examples are given for the purpose ofillustrating the present invention.

Preparation 1

To a solution of 1-(4-methylphenyl)pyrrole-2-carbonitrile (1.274 g) intetrahydrofuran (25 ml) was added N-bromosuccinimide (1.776 g) inseveral portions at ambient temperature. After being stirred for 3 hoursat the same temperature, the mixture was concentrated in vacuo. Theresidue was treated with diethyl ether. The precipitates were removed byfiltration and washed with a small amounts of diethyl ether. Thefiltrates were concentrated in vacuo to give an oily residue, which waspurified by silica gel column chromatography (elution by 40%dichloromethane in n-hexane) to yield4-bromo-1-(4-methylphenyl)pyrrole-2-carbonitrile (1.78 g) as a solid.

mp: 55°-59.5° C.

NMR (CDCl₃, δ): 2.42 (3H, s), 6.93 (1H, d, J=2.3 Hz), 7.04 (1H, d, J=2.3Hz), 7.29 (5H, s)

Preparation 2

To a solution of 1-(4-methylphenyl)pyrrole (1 g) in tetrahydrofuran (50ml) was added N-chlorosuccinimide (850 mg) in one portion at -78° C.under nitrogen atmosphere. The mixture was warmed to 10° C., stirred forone hour, and then concentrated in vacuo. The residue was purified byflash column chromatography on silica gel to yield2-chloro-1-(4-methylphenyl)pyrrole (1.2 g) as an oil. (This product wasa mixture of the starting material and the desired product and used tothe next reaction furthermore without purification.)

Preparation 3

Phosphoryl chloride (747 μl) was added dropwise to N,N-dimethylformamide(7 ml) at 5° C. The mixture was stirred at 5° C. for 15 minutes and atambient temperature for 15 minutes. To the mixture was added a solutionof 2-chloro-1-(4-methylphenyl)pyrrole (1.2 g) in N,N-dimethylformamide(7 ml) at ambient temperature. The mixture was stirred at the sametemperature for one hour and at 50° C. for 2.5 hours. After cooled toambient temperature, the mixture was treated with saturated aqueoussodium bicarbonate solution. The separated oil was extracted with ethylacetate. The organic layer was washed with water, dried, andconcentrated in vacuo. The residue was column chromatographed on silicagel to yield 5-chloro-1-(4-methylphenyl)pyrrole-2-carbaldehyde (377 mg)as a solid.

NMR (CDCl₃, δ): 2.44 (3H, s), 6.33 (1H, d, J=4.5 Hz), 7.09 (1H, d, J=4.5Hz), 7.18 (2H, d, J=8.0 Hz), 7.31 (2H, d, J=8.0 Hz), 9.32 (1H, s)

Preparation 4

A mixture of 5-chloro-1-(4-methylphenyl)pyrrole-2-carbaldehyde (365 mg),hydroxylamine hydrochloride (173 mg), and sodium acetate (204 mg) in 60%aqueous ethanol (6 ml) was stirred at 60° C. for one hour. The mixturewas concentrated in vacuo. The residue was dissolved in ethyl acetate.The mixture was washed with water, dried, and concentrated in vacuo togive a residue (450 mg) of5-chloro-1-(4-methylphenyl)pyrrole-2-carbaldehyde oxime. A mixture ofthe residue and sodium acetate (30 mg) in acetic anhydride (5 ml) wasstirred at 160° C. for one and half hours under nitrogen atmosphere. Thereaction mixture was concentrated in vacuo. The residue was purified bysilica gel column chromatography (eluted by ethyl acetate:n-hexane=1/15) to yield 5-chloro-1-(4-methylphenyl)pyrrole-2-carbonitrile (325mg) as an oil.

NMR (CDCl₃, δ): 2.45 (3H, s), 6.25 (1H, d, J=4.5 Hz), 6.90 (1H, d, J=4.5Hz), 7.23 (2H, d, J=8.0 Hz), 7.34 (2H, d, J=8 Hz)

Preparation 5

To a solution of 1-(4-methylphenyl)pyrrole-2-carbonitrile (1.092 g) in amixture of ethanol (10 ml) and 1,4-dioxane (10 ml) was addedN-chlorosuccinimide (1.862 g) in one portion at ambient temperature. Themixture was stirred for 2.5 hours at the same temperature and then water(30 ml) was added therein. The separated oil was extracted with diethylether. The extract was washed with water, dried, and concentrated invacuo. The yellow residue was crystallized from n-hexane to yield3,4-dichloro-1-(4-methylphenyl)pyrrole-2-carbonitrile (1.28 g).

mp: 85°-86° C.

NMR (CDCl₃, δ): 2.45 (3H, s), 6.91 (1H, s), 7.23 and 7.34 (4H, ABq,J=7.5 Hz)

Preparation 6

To a solution of 1-(4-methylphenyl)pyrrole-2-carbonitrile (1.0 g) inacetic anhydride (4 ml) was added nitric acid (231 μl, 94%) dropwise at5° C. The mixture was stirred at the same temperature for 3 hours andthen poured into ice water. The pH was adjusted to 5-7 by the additionof saturated aqueous sodium bicarbonate solution. The separated oil wasextracted with ethyl acetate The organic layer was washed with saturatedaqueous sodium bicarbonate solution, water and brine, dried, andevaporated under reduced pressure. The residue was purified by silicagel column chromatography to yield1-(4-methylphenyl)-4-nitropyrrole-2-carbonitrile (471 mg) as a solid.

NMR (CDCl₃, δ): 2.47 (3H, s), 7.36 (4H, s), 7.49 (1H, d, J=1.5 Hz), 7.83(1H, d, J=1.5 Hz)

Preparation 7

A mixture of 3,4-dichloro-1-(4-methylphenyl)pyrrole-2-carbonitrile (1.25g), 2,2'-azobisisobutyronitrile (10 mg) and N-bromosuccinimide (1.068 g)in carbon tetrachloride (25 ml) was refluxed for 3 hours, cooled toambient temperature, and filtered. The filtrate was concentrated invacuo. The residue was crystallized from 10% ethyl acetate in n-hexaneto yield 1-(4-bromomethylphenyl)-3,4-dichloropyrrole-2-carbonitrile(1.01 g).

NMR (CDCl₃, δ): 4.53 (2H, s), 6.94 (1H, s), 7.46 and 7.58 (4H, ABq,J=7.5 Hz)

Preparation 8

The following compounds were obtained according to a similar manner tothat of Preparation 7.

(1) 4-Bromo-1-(4-bromomethylphenyl)pyrrole-2-carbonitrile mp: 105°-116°C.

NMR (CDCl₃, δ): 4.54 (2H, s), 7.00 (1H, d, J=2.3 Hz), 7.10 (1H, d, J=2.3Hz), 7.41 (2H, d, J=8.5 Hz), 7.55 (2H, d, J=8.5 Hz)

(2) 1-(4-Bromomethylphenyl)-5-chloropyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.53 (2H, s), 6.30 (1H, d, J=4.5 Hz), 6.94 (1H, d, J=4.5Hz), 7.37 (2H, d, J=8.0 Hz), 7.57 (2H, d, J=8.0 Hz)

(3) 1-(4-Bromomethylphenyl)-4-nitropyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.54 (2H, s), 7.48 (2H, d, J=8.5 Hz), 7.52 (1H, d, J=1.5Hz), 7.62 (2H, d, J=8.5 Hz), 7.88 (1H, d, J=1.5 Hz)

(4) 1-(4-Bromomethylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.55 (2H, s), 6.37 (1H, dd, J=4.5 Hz and 3.0 Hz), 7.01(1H, dd, J=4.5 Hz and 2.5 Hz), 7.09 (1H, dd, J=3 Hz and 2.5 Hz), 7.43(2H, d, J=9 Hz), 7.52 (2H, d, J=9 Hz)

(5) 1-(4-Bromomethylphenyl)indole-2-carbonitrile

This compound was used to the next reaction without furthermorepurification.

Preparation 9

To a solution of 2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine (568 mg) indimethyl sulfoxide (7 ml) was added sodium hydride (132 mg, 60% oildispersion) at ambient temperature. The mixture was stirred for 40minutes at the same temperature. To the mixture was added dropwise asolution of 1-(4-bromomethylphenyl)-3,4-dichloropyrrole-2-carbonitrile(990 mg) in dimethyl sulfoxide (3 ml). The mixture was stirred for 2hours at ambient temperature and ice water (30 ml) was added therein.The separated oil was extracted twice with ethyl acetate. The extractswere washed with water, dried, and evaporated under reduced pressure.The residue was purified by silica gel column chromatography eluted by50% ethyl acetate in n-hexane to give2-butyl-3-[4-(2-cyano-3,4-dichloro-1-pyrrolyl)benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine(546 mg) as an oil.

NMR (CDCl₃, δ): 0.91 (3H, t, J=7.5 Hz), 1.42 (2H, m), 1.76 (2H, m), 2.73(3H, s), 2.90 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.94 (1H, s), 7.09 (1H,d, J=5 Hz), 7.31 (4H, s), 8.25 (1H, d, J=5 Hz)

Preparation 10

The following compounds were obtained according to a similar manner tothat of Preparation 9.

(1)3-[4-(4-Bromo-2-cyano-1-pyrrolyl)benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.92 (3H, t, J=7.5 Hz), 1.42 (2H, m), 1.77 (2H, m), 2.72(3H, s), 2.88 (2H, t, J=7.5 Hz), 5.57 (2H, s), 6.97 (1H, d, J=2.3 Hz),7.03 (1H, d, J=2.3 Hz), 7.08 (1H, d, J=5 Hz), 7.38 (2H, d, J=8.5 Hz),7.48 (2H, d, J=8.5 Hz), 8.24 (1H, d, J=5 Hz)

(2)2-Butyl-3-[4-(5-chloro-2-cyano-1-pyrrolyl)benzyl]-3H-imidazo[4,5-b]pyridin

NMR (CDCl , 6): 0.92 (3H, t, J=7.5 Hz), 1.32-1.52 (2H, m), 1.72-1.91(2H, m), 2.87 (2H, t, J=7.5 Hz), 5.59 (2H, s), 6.27 (1H, d, J=4.5 Hz),6.91 (1H, d, J=4.5 Hz), 7.28 (1H, dd, J=8.5 Hz and 5.0 Hz), 7.32 (4H,s), 8.07 (1H, dd, J=8.5 Hz and 1.0 Hz), 8.38 (1H, dd, J=5.0 Hz and 1.0Hz)

(3)2-Butyl-3-[4-(2-cyano-4-nitro-1-pyrrolyl)benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.94 (3H, t, J=7.5 Hz), 1.33-1.56 (2H, m), 1.77-1.97(2H, m), 2.90 (2H, t, J=7.5 Hz), 5.61 (2H, s), 7.31 (1H, dd, J=7.5 Hzand 4.5 Hz), 7.37 (2H, d, J=8.5 Hz), 7.45 (2H, d, J=8.5 Hz), 7.49 (1H,d, J=1.5 Hz), 7.82 (1H, d, J=1.5 Hz), 8.09 (1H, dd, J=7.5 Hz and 1Hz),8.39 (1H, dd, J=4.5 Hz and 1.0 Hz)

(4) 2-Butyl-3-[4-(2-cyano-1-pyrrolyl)benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.93 (3H, t, J=7.5 Hz), 1.45 (2H, m), 1.87 (2H, m), 2.88(2H, dd, J=8 Hz and 8 Hz), 5.56 (2H, s), 6.33 (1H, dd, J=4 Hz and 3 Hz),6.98 (1H, dd, J=4 Hz and 1Hz), 7.03 (1H, dd, J=3 Hz and 1Hz), 7.28 (1H,m), 7.29 (2H, d, J=8 Hz), 7.41 (2H, d, J=8 Hz), 8.07 (1H, dd, J=7.5 Hzand 1.5 Hz), 8.38 (1H, dd, J=4 Hz and 1.5 Hz)

(5) 2-Butyl-3-[4-(2-cyano-1-indolyl)benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.93 (3H, t, J=7.5 Hz), 1.46 (2H, m), 1.88 (2H, m), 2.98(2H, t, J=8 Hz), 5.66 (2H, s), 7.21-7.45 (4H, m), 7.32 (2H, d, J=8 Hz),7.40 (1H, s), 7.48 (2H, d, J=8 Hz), 7.72 (1H, m), 8.13 (1H, dd, J=8 Hzand 1Hz), 8.46 (1H, dd, J=4.5 Hz and 1Hz)

(6)2-Butyl-3-[4-(5-chloro-2-cyano-1-pyrrolyl)benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.90 (3H, t, J=6.5 Hz), 1.40 (2H, m), 1.73 (2H, m), 2.72(3H, s), 2.87 (2H, t, J=7.5 Hz), 5.58 (2H, s), 6.24 (1H, d, J=4 Hz),6.90 (1H, d, J=4 Hz), 7.08 (1H, d, J=5 Hz), 7.30 (4H, s), 8.25 (1H, d,J=5 Hz)

Preparation 11

A mixture of 2-amino-4-methyl-3-nitropyridine (5.0 g) andN,N-dimethylaniline (8.5 ml) was heated at 100° C. under nitrogenatmosphere. To the solution was added butyryl chloride (3.5 ml) and themixture was stirred at 100° C. for 5 hours. After being cooled to roomtemperature, ethyl acetate was added to the reaction mixture. Theorganic layer was separated and washed successively with water andbrine. The solution was dried over magnesium sulfate and the solvent wasevaporated in vacuo. The residue was washed with n-hexane to give2-butyrylamino-4-methyl-3-nitropyridine (7.0 g).

mp: 92.5°-99° C.

NMR (CDCl₃, δ): 1.01 (3H, t, J=7.5 Hz), 1.64-1.85 (2H, m), 2.43 (2H, t,J=7.5 Hz), 2.48 (3H, s), 7.10 (1H, d, J=5.0 Hz), 8.26 (1H, br s), 8.35(1H, d, J=5.0 Hz)

Preparation 12

A solution of 2-butyrylamino-4-methyl-3-nitropyridine (7.0 g) and ironpowder (17.5 g) in a mixture of acetic acid (14 ml) and ethanol (100 ml)was stirred at 90° C. for 3 hours under nitrogen atmosphere. After beingcooled to room temperature, the reaction mixture was filtered throughCelite and the filtrate was evaporated in vacuo. Ethyl acetate andsaturated aqueous sodium hydrogencarbonate were added to the residueuntil pH 7˜8 and the resulting suspension was filtered through Celite.The organic layer of the filtrate was separated, washed with brine anddried over magnesium sulfate. The solvent was evaporated in vacuo andthe residue was purified with silica gel column chromatography (eluent:ethyl acetate) to give 7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine (3.6g).

mp: 108°-111° C.

NMR (CDCl₃, δ): 1.09 (3H, t, J=7.5 Hz), 1.90-2.12 (2H, m), 2.72 (3H, s),3.06 (2H, t, J=7.5 Hz), 7.07 (1H, d, J=5.0 Hz), 8.19 (1H, d, J=5.0 Hz)

Preparation 13

2-Bromo-4-methylaniline (15.0 g), 2,5-dimethoxytetrahydrofuran (10.7 g)and acetic acid (81 ml) were combined under nitrogen atmosphere. Thereaction mixture was stirred at 90° C. for 1.5 hours. After being cooledto room temperature, the reaction mixture was concentrated in vacuo withtoluene. n-Hexane (300 ml) was added to the residue, and the suspensionwas filtered through Celite. Then silica gel was added to the filtratewith stirring until the colour of the solution disappeared. Thesuspension was filtered and the filtrate was concentrated in vacuo togive 1-(2-bromo-4-methylphenyl)pyrrole (16.1 g).

NMR (CDCl₃, δ): 2.38 (3H, s), 6.31 (2H, t, J=3.0 Hz), 6.83 (2H, t, J=3.0Hz), 7.12-7.22 (2H, m), 7.51 (1H, d, J=1.0 Hz)

Preparation 14

The following compounds were obtained according to a similar manner tothat of Preparation 13.

(1) 1-(3-Fluoro-4-methylphenyl)pyrrole

NMR (CDCl₃, δ): 2.39 (3H, d, J=2.5 Hz), 6.32 (2H, m), 7.02-7.26 (5H, m)

(2) 5-Methyl-2-(1-pyrrolyl)pyridine

mp: 54.5°-62° C.

NMR (CDCl₃, δ): 2.33 (3H, s), 6.35 (2H, t, J=2.0 Hz), 7.22 (1H, d, J=8.5Hz), 7.48 (2H, t, J=2.0 Hz), 7.56 (1H, dd, J=8.5 Hz, 1.5 Hz), 8.25 (1H,d, J=1.5 Hz)

(3) 1-(3-Chloro-4-methylphenyl)pyrrole

mp: 48°-50° C.

NMR (CDCl₃, δ): 2.39 (3H, s), 6.34 (2H, dd, J=4 Hz, 4 Hz), 7.05 (2H, dd,J=4 Hz, 4 Hz), 7.19 (1H, dd, J=8 Hz, 2 Hz), 7.26 (1H, d, J=8 Hz), 7.40(1H, d, J=2 Hz)

(4) 1-(3-Methoxy-4-methylphenyl)pyrrole

NMR (CDCl₃, δ): 2.23 (3H, s), 3.87 (3H, s), 6.33 (2H, t, J=2 Hz), 6.84(1H, d, J=2 Hz), 6.88 (1H, dd, J=8 Hz, 2 Hz), 7.06 (2H, t, J=2 Hz), 7.16(1H, d, J=8 Hz)

(5) 1-(4-Methyl-2-nitrophenyl)pyrrole

NMR (CDCl₃, δ): 2.48 (3H, s), 6.35 (2H, t, J=2 Hz), 6.78 (2H, t, J=2Hz), 7.35 (1H, d, J=8 Hz), 7.46 (1H, dd, J=8 Hz, 1Hz), 7.67 (1H, d,J=1Hz)

(6) 1-(2-Chloro-4-methylphenyl)pyrrole

NMR (CDCl₃, δ): 2.48 (3H, s), 6.34 (2H, t, J=2.5 Hz), 6.89 (2H, t, J=2.5Hz), 7.12 (1H, dd, J=9 Hz, 1Hz), 7.24 (1H, d, J=9 Hz), 7.33 (1H, br s)

Preparation 15

The following compounds were obtained according to a similar manner tothat of Preparation 3.

(1) 1-(5-Methyl-2-pyridyl)pyrrole-2-carbaldehyde

NMR (CDCl₃, δ): 2.40 (3H, s), 6.42 (1H, dd, J=4.0 Hz, 3.5 Hz), 7.19 (1H,dd, J=4.0 Hz, 1.5 Hz), 7.33 (1H, d, J=8.5 Hz), 7.41 (1H, dd, J=3.5 Hz,1.5 Hz), 7.64 (1H, dd, J=8.5 Hz, 2.0 Hz), 8.33 (1H, d, J=2.0 Hz), 9.75(1H, s)

(2) 1-(3-Chloro-4-methylphenyl)pyrrole-2-carbaldehyde

NMR (CDCl₃, δ): 2.44 (3H, s), 6.41 (1H, dd, J=4 Hz, 3 Hz), 7.04 (1H, m),7.15 (1H, m), 7.17 (1H, dd, J=7 Hz, 2 Hz), 7.32 (1H, d, J=7 Hz), 7.37(1H, d, J=2 Hz), 9.48 (1H, s)

(3) 1-(3-Methoxy-4-methylphenyl)pyrrole-2-carbaldehyde

NMR (CDCl₃, δ): 2.27 (3H, s), 3.85 (3H, s), 6.40 (1H, dd, J=4 Hz, 3 Hz),6.82 (1H, d, J=2 Hz), 6.87 (1H, dd, J=7 Hz, 2 Hz), 7.08 (1H, dd, J=3 Hz,2 Hz), 7.17 (1H, dd, J=4 Hz, 2 Hz), 7.20 (1H, d, J=7 Hz), 9.59 (1H, s)

(4) 1-(2-Chloro-4-methylphenyl)pyrrole-2-carbaldehyde

mp: 109°-110° C.

NMR (CDCl , 6): 2.42 (3H, s), 6.43 (1H, dd, J=4 Hz, 3 Hz), 6.95 (1H, m),7.11 (1H, dd, J=4 Hz, 1Hz), 7.19 (1H, d, J=9 Hz), 7.15 (1H, d, J=9 Hz),7.32 (1H, br s), 9.50 (1H, s)

Preparation 16

1-(4-Methylphenyl)pyrrole-2-carbaldehyde (1.45 g) was dissolved inchloroform (20 ml), and pyridinium hydrobromide perbromide (2.62 g) wasadded to the solution at 0° C. under nitrogen atmosphere. The reactionmixture was stirred at the same temperature for 30 minutes. Methylenechloride was added to the mixture, and then saturated sodium thiosulfatewas added until excess reagent was decomposed. The organic solution waswashed with saturated sodium hydrogencarbonate and brine, and dried overmagnesium sulfate. The obtained residue was purified by isopropyl etherto give 1-bromo-1-(4-methylphenyl)pyrrole-2-carbaldehyde (1.65 g).

NMR (CDCl₃, δ): 2.47 (3H, s), 6.46 (1H, d, J=4 Hz), 7.09 (1H, d, J=4Hz), 7.17 (2H, d, J=8 Hz), 7.30 (2H, d, J=8 Hz)

Preparation 17

The following compounds were obtained according to a similar manner tothat of Preparation 16.

(1) 5-Bromo-1-(5-methyl-2-pyridyl)pyrrole-2-carbaldehyde

mp: 65 5°-73° C.

NMR (CDCl₃, δ): 2.45 (3H, s), 6.47 (1H, d, J=4.5 Hz), 7.07 (1H, d, J=4.5Hz), 7.24 (1H, d, J=7.0 Hz), 7.71 (1H, dd, J=7.0 Hz, 1.5 Hz), 8.04 (1H,d, J=1.5 Hz), 9.37 (1H, s)

(2) 5-Bromo-1-(2-chloro-4-methylphenyl)pyrrole-2-carbaldehyde

NMR (CDCl₃, δ): 2.44 (3H, s), 6.50 (1H, d, J=4 Hz), 7.06 (1H, d, J=4Hz), 7.20 (2H, s), 7.36 (1H, br s), 9.29 (1H, s)

(3) 5.Bromo-1-(3-methoxy-4-methylphenyl)pyrrole-2-carbaldehyde

NMR (CDCl₃, δ): 2.30 (3H, s), 3.33 (3H, s), 6.47 (1H, d, J=4 Hz), 6.71(1H, d, J=2 Hz), 6.80 (1H, dd, J=8, 2 Hz), 7.10 (1H, d, J=4 Hz), 7.24(1H, d, J=8 Hz), 9.31 (1H, s)

Preparation 18

The following compounds were obtained according to a similar manner tothat of Preparation 4.

(1) 5-Bromo-1-(4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.44 (3H, s), 6.37 (1H, d, J=4 Hz), 6.92 (1H, d, J=4Hz), 7.23 (2H, d, J=8 Hz), 7.32 (2H, d, J=8 Hz)

(2) 1-(5-Mehyl-2pyridyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.39 (3H, s), 6.37 (1H, t, J=4.5 Hz), 7.04 (1H, dd,J=4.5 Hz, 1.0 Hz), 7.52 (1H, d, J=9.0 Hz), 7.56 (1H, dd, J=4.5 Hz, 1.0Hz), 7.69 (1H, dd, J=9.0 Hz, 1.5 Hz), 8.39 (1H, d, J=1.5 Hz)

(3) 5-Bromo-1-(5-methyl-2-pyridyl)pyrrole-2-carbonitrile

mp: 95°-100.5° C.

NMR (CDCl₃, δ): 2.45 (3H, s), 6.40 (1H, d, J=4.0 Hz), 6.95 (1H, d, J=4.0Hz), 7.37 (1H, d, J=8.5 Hz), 7.73 (1H, dd, J=8.5 Hz, 1.5 Hz), 8.48 (1H,d, J=1.5 Hz)

(4) 5-Bromo-1-(2-chloro-4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.46 (3H, s), 6.40 (1H, d, J=4 Hz), 6.94 (1H, d, J=4Hz), 7.20-7.94 (2H, m), 7.41 (1H, br s)

(5) 1-(3-Chloro-4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.42 (3H, s), 6.35 (1H, dd, J=4 Hz, 2.5 Hz), 6.99 (1H,dd, J=4 Hz, 1Hz), 7.05 (1H, dd, J=2.5 Hz, 1Hz), 7.28 (1H, dd, J=8 Hz,1.5 Hz), 7.36 (1H, d, J=8 Hz), 7.45 (1H, d, J=1.5 Hz)

(6) 5-Bromo-1-(3-methoxy-4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.30 (3H, s), 3.89 (3H, s), 6.40 (1H, d, J=4 Hz), 6.78(1H, d, J=2 Hz), 6.88 (1H, dd, J=8, 2 Hz), 6.94 (1H, d, J=4 Hz), 7.38(1H, d, J=8 Hz)

(7) 1-(2-Chloro-4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.42 (3H, s), 6.35 (1H, dd, J=4 Hz, 3 Hz), 6.89-7.02(2H, m), 7.18 (1H, dd, J=8 Hz, 1Hz), 7.28 (1H, d, J=8 Hz), 7.36 (1H, brs)

Preparation 19

Chlorosulfonyl isocyanate (1.2 ml) in methylene chloride (12 ml) wasadded dropwise to a stirred solution of1-(2-bromo-4-methylphenyl)pyrrole (2.5 g) in methylene chloride (25 ml)kept about -20° C. under nitrogen atmosphere. The reaction mixture wasstirred at -20° C. for 30 minutes and at room temperature for 1.5 hours,and then was added dropwise dimethylformamide (1.7 ml) keeping at about-20° C. The reaction mixture was stirred at -20° C. for 30 minutes andat room temperature for an hour. To the reaction mixture was added4N-hydrochloric acid at 0° C., and stirred at 0° C. for 30 minutes. Theorganic layer was washed with water and saturated sodiumhydrogencarbonate solution, and dried over magnesium sulfate, andevaporated in vacuo. The residue was purified by silica gel columnchromatography with a mixture of ethyl acetate and n-hexane (1:10) aseluent to give 1-(2-bromo-4-methylphenyl)pyrrole-2-carbonitrile (2.4 g).

NMR (CDCl₃, δ): 2.42 (3H, s), 6.36 (1H, dd, J=4.0, 3.0 Hz), 6.93 (1H,dd, J=3.0 Hz, 1.0 Hz), 6.97 (1H, dd, J=4.0 Hz, 1.0 Hz), 7.22-7.29 (2H,m), 7.55 (1H, d, J=1.0 Hz)

Preparation 20

The following compounds were obtained according to a similar manner tothat of Preparation 19.

(1) 1-(3-Fluoro-4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.35 (3H, d, J=2.5 Hz), 6.37 (1H, m), 6.99-7.48 (5H, m)

(2) 1-(4-Methyl-2-nitrophenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, ε): 2.56 (3H, s), 6.48 (1H, dd, J=4 Hz, 3 Hz), 6.90 (1H, dd,J=3 Hz, 2 Hz), 7.01 (1H, dd, J=4 Hz, 2 Hz), 7.41 (1H, d, J=8 Hz), 7.57(1H, dd, J=8 Hz, 1Hz), 7.92 (1H, d, J=1Hz)

Preparation 21

The following compounds were obtained according to a similar manner tothat of Preparation 2.

(1) 4-Bromo-3-chloro-1-(4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.47 (3H, s), 6.97 (1H, s), 7.23 (2H, d, J=9 Hz), 7.35(2H, d, J=9 Hz)

(2) 4-Bromo-1-(3-fluoro-4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.35 (3H, d, J=2.5 Hz), 6.88 (1H, d, J=2 Hz), 7.07 (1H,d, J=2 Hz), 7.09-7.49 (4H, m)

(3) 4-Bromo-1-(2-bromo-4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.41 (3H, s), 6.93 (2H, s), 7.23-7.28 (2H, m), 7.56 (1H,s)

(4) 4-Bromo-1-(2-chloro-4-methylphenyl)pyrrole-2-carbonitrile

mp: 92°-94° C.

NMR (CDCl₃, δ): 2.42 (3H, s), 6.94 (2H, s), 7.19 (1H, dd, J=7.5 Hz, 0.8Hz), 7.27 (1H, d, J=7.5 Hz), 7.36 (1H, m)

(5) 4-Bromo-1-(3-chloro-4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.43 (3H, s), 6.96 (1H, d, J=2 Hz), 7.06 (1H, d, J=2Hz), 7.26 (1H, dd, J=8 Hz, 2 Hz), 7.35 (1H, d, J=8 Hz), 7.42 (1H, d, J=2Hz)

Preparation 22

The following compounds were obtained according to a similar manner tothat of Preparation 7.

(1) 4-Bromo-1-(4-bromomethylphenyl)-3-chloropyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.55 (2H, s), 7.00 (1H, s), 7.34 (2H, d, J=9 Hz), 7.59(2H, d, J=9 Hz)

(2) 5-Bromo-1-(4-bromomethylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.55 (2H, s), 6.40 (1H, d, J=4 Hz), 6.93 (1H, d, J=4Hz), 7.33 (1H, d, J=8 Hz), 7.55 (1H, d, J=8 Hz)

(3) 4-Bromo-1-(4-bromomethyl-3-fluorophenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.54 (2H, s), 7.01 (1H, d, J=2.5 Hz),7.10 (1H, d, J=2.5Hz), 7.19-7.62 (3H, m)

(4) 1-(5-Bromomethyl-2-pyridyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.52 (2H, s), 6.40 (1H, t, J=4.0 Hz), 7.08 (1H, dd,J=4.0 Hz, 1.0 Hz), 7.61 (1H, dd, J=4.0 Hz, 1.0 Hz), 7.65 (1H, d, J=9.0Hz), 7.92 (1H, dd, J=9.0 Hz, 2.0 Hz), 8.54 (1H, d, J=2.0 Hz)

(5) 5-Bromo-1-(5-bromomethyl-2-pyridyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.54 (2H, s), 6.42 (1H, d, J=4.5 Hz), 6.97 (1H, d, J=4.5Hz), 7.49 (1H, d, J=8.5 Hz), 7.98 (1H, dd, J=8.5 Hz, 1.5 Hz), 8.68 (1H,d, J=1.5 Hz)

(6) 1-(2-Bromo-4-bromomethylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.49 (2H, s), 6.38 (1H, dd, J=4.0 Hz, 3.0 Hz), 6.93-7.03(2H, m), 7.39 (1H, d, J=8.0 Hz), 7.49 (1H, dd, J=8.0 Hz, 1.0 Hz), 7.77(1H, d, J=1.0 Hz)

(7) 4-Bromo-1-(2-bromo-4-bromomethylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.48 (2H, s), 6.97 (2H, s), 7.35 (1H, d, J=8.0 Hz), 7.49(1H, dd, J=8.0 Hz, 1.0 Hz), 7.79 (1H, d, J=1.0 Hz)

(8) 5-Bromo-1-(4-bromomethyl-2-chlorophenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.50 (2H, s), 6.42 (1H, d, J=4 Hz), 6.95 (1H, d, J=4Hz), 7.36 (1H, d, J=8 Hz), 7.47 (1H, d, J=8 Hz, 1Hz), 7.62 (1H, d,J=1Hz)

(9) 4-Bromo-1-(4-bromomethyl-2-chlorophenyl)pyrrole-2-carbonitrile

(This product was a mixture of the starting material and the desiredproduct and used to the next reaction furthermore without purification.)

(10) 4-Bromo-1-(4-bromomethyl-3-chlorophenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.61 (2H, s), 6.99 (1H, d, J=1.5 Hz), 7.19 (1H, d, J=1.5Hz), 7.36 (1H, dd, J=8 Hz and 2 Hz), 7.50 (1H, d, J=2 Hz), 7.61 (1H, d,J=8 Hz)

(11) 5-Bromo-1-(4-bromomethyl-3-methoxyphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 3.94 (3H, s), 4.58 (2H, s), 6.49 (1H, d, J=4 Hz), 6.85(1H, d, J=2 Hz), 6.90-6.99 (2H, m), 7.48 (1H, d, J=8 Hz)

(12) 1-(4-Bromomethyl-2-nitrophenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.57 (2H, s), 6.41 (1H, dd, J=4.3 Hz), 6.91 (1H, dd,J=3, 2 Hz), 7.03 (1H, dd, J=4 Hz, 2 Hz), 7.53 (1H, d, J=8 Hz), 7.80 (1H,dd, J=8 Hz, 2 Hz), 8.14 (1H, d, J=2 Hz)

(13) 1-(4-Bromomethyl-2-chlorophenyl)pyrrole-2-carbonitrile

(This product was a mixture of the starting material and the desiredproduct and used to the next reaction furthermore without purification.)

Preparation 23

The following compounds were obtained according to a similar manner tothat of Preparation 9.

(1) 3-[4-(4-Bromo-3-chloro-2-cyano-1-pyrrolyl)benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.90 (3H, t, J=7 Hz), 1.40 (2H, m), 1.74 (2H, m), 2.71(3H, s), 2.86 (2H, t, J=8 Hz), 5.59 (2H, s), 6.96 (1H, s), 7.07 (1H, d,J=5 Hz), 7.30 (4H, s), 8.23 (1H, d, J=5 Hz)

(2)3-[4-(2-Bromo-5-cyano-1-pyrrolyl)benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.90 (3H, t, J=7.5 Hz), 1.41 (2H, m), 1.74 (2H, m), 2.70(3H, s), 2.88 (2H, t, J=8 Hz), 5.60 (2H, s), 6.37 (1H, d, J=4 Hz), 6.91(1H, d, J=4 Hz), 7.07 (1H, d, J=5 Hz), 7.31 (4H, s), 8.24 (1H, d, J=5Hz)

(3)3-[4-(4-Bromo-2-cyano-1-pyrrolyl)]-2-fluorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.92 (3H, t, J=7.5 Hz), 1.33-1.56 (2H, m), 1.68-1.87(2H, m), 2.70 (3H, s), 2.89 (2H, t, J=7.5 Hz), 5.58 (2H, s), 6.97 (1H,d, J=1 0 Hz), 7.01-7.30 (5H, m), 8.21 (1H, d, J=5.0 Hz)

(4)3-[4-(4-Bromo-2-cyano-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 115°-118° C.

NMR (CDCl₃, δ): 1.01 (3H, t, J=7.5 Hz), 1.71-1.93 (2H, m), 2.71 (3H, s),2.85 (2H, t, J=7.5 Hz), 5.57 (2H, s), 6.96 (1H, d, J=1.5 Hz), 7.03 (1H,d, J=1.5 Hz), 7.07 (1H, d, J=5.0 Hz), 7.28 (2H, d, J=9.5 Hz), 7.38 (2H,d, J=9.5 Hz), 8.22 (1H, d, J=5.0 Hz)

(5)2-Butyl-3-[2-(2-cyano-1-pyrrolyl)-5-pyridylmethyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 104°-108.5° C.

NMR (CDCl₃, δ): 0.93 (3H, t, J=7.5 Hz), 1.34-1.55 (2H, m), 1.69-1.89(2H, m), 2.70 (3H, s), 2.89 (2H, t, J=7.5 Hz), 5.53 (2H, s), 6.37 (1H,dd, J=4.5 Hz, 3.0 Hz), 7.01-7.11 (2H, m), 7.54 (1H, dd, J=3.0 Hz, 1.0Hz), 7.56 (1H, d, J=8.0 Hz), 7.70 (1H, dd, J=8.0 Hz, 1.5 Hz), 8.22 (1H,d, J=5.0 Hz), 8.46 (1H, d, J=1.5 Hz)

(6)3-[2-(5-Bromo-2-cyano-1-pyrrolyl)-5-pyridylmethyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.92 (3H, t, J=7.5 Hz), 3.33-1.54 (2H, m), 1.68-1.86(2H, m), 2.70 (3H, s), 2.89 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.40 (1H,d, J=4.0 Hz), 6.95 (1H, d, J=4.0 Hz), 7.07 (1H, d, J=5.0 Hz), 7.39 (1H,d, J=8.5 Hz), 7.71 (1H, dd, J=8.5 Hz, 1.5 Hz), 8.23 (1H, d, J=5.0 Hz),8.61 (1H, d, J=1.5 Hz)

(7)3-[3-Bromo-4-(2-cyano-1-pyrrolyl)benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp 162°-167° C.

NMR (CDCl₃, δ): 0.94 (3H, t, J=7.5 Hz), 1.35-1.56 (2H, m), 1.70-1.88(2H, m), 2.71 (3H, s), 2.89 (2H, t, J=7.5 Hz), 5.53 (2H, s), 6.35 (1H,dd, J=3.5 Hz, 3.0 Hz), 6.90 (1H, dd, J=3.0 Hz, 1.0 Hz), 6.98 (1H, dd,J=3.5 Hz, 1.0 Hz), 7.08 (1H, d, J=5.0 Hz), 7.18 (1H, dd, J=8.0 Hz, 1.0Hz), 7.35 (1H, d, J=8.0 Hz), 7.53 (1H, d, J=1.0 Hz), 8.22 (1H, d, J=5.0Hz)

(8)3-[3-Bromo-4-(4-bromo-2-cyano-1-pyrrolyl)benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.93 (3H, t, J=7.5 Hz), 1.34-1.55 (2H, m), 1.70-1.91(2H, m), 2.73 (3H, s), 2.93 (2H, t, J=7.5 Hz), 5.54 (2H, s), 6.90 (1H,d, J=1.0 Hz), 6.94 (1H, d, J=1.0 Hz), 7.10 (1H, d, J=5.0 Hz), 7.18 (1H,dd, J=8.0 Hz, 1.0 Hz), 7.32 (1H, d, J=8.0 Hz), 7.56 (1H, d, J=1.0 Hz),8.23 (1H, d, J=5.0 Hz)

(9)3-[4-(2-Bromo-5-cyano-1-pyrrolyl)-3-chlorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.91 (3H, t, J=7 Hz), 1.42 (2H, m), 1.75 (2H, m), 2.73(3H, s), 2.88 (2H, t, J=8 Hz), 5.58 (2H, s), 6.40 (1H, d, J=4 Hz), 6.92(1H, d, J=4 Hz), 7.09 (1H, d, J=5 Hz), 7.19 (1H, dd, J=8 Hz, 1Hz), 7.31(1H, d, J=8 Hz), 7.39 (1H, d, J=1Hz), 8.25 (1H, d, J=5 Hz)

(10)3-[4-(4-Bromo-2-cyano-1-pyrrolyl)-3-chlorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.92 (3H, t, J=8 Hz), 1.45 (2H, m), 1.79 (2H, m), 2.73(3H, s), 2.89 (2H, t, J=8 Hz), 5.55 (2H, s), 6.92 (1H, d, J=1Hz), 6.95(1H, d, J=1Hz), 7.07 (1H, d, J=5 Hz), 7.15 (1H, dd, J=7.5 Hz, 1Hz), 7.34(1H, d, J=7.5 Hz), 7.36 (1H, s), 8.22 (1H, d, J=5 Hz)

(11)3-[4-(4-Bromo-2-cyano-1-pyrrolyl)-2-chlorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.92 (3H, t, J=8 Hz), 1.49 (2H, m), 1.78 (2H, m), 2.80(3H, s), 3.00 (2H, m), 5.70 (2H, s), 6.77 (1H, d, J=8 Hz), 6.99 (1H, d,J=2 Hz), 7.04 (1H, d, J=2 Hz), 7.20 (1H, dd, J=8 Hz, 2 Hz), 7.25 (1H, d,J=8 Hz), 7.58 (1H, d, J=2 Hz), 8.30 (1H, d, J=8 Hz)

(12)3-[4-(2-Bromo-5-cyano-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.99 (3H, t, J=7 Hz), 1.80 (2H, m), 2.70 (3H, s), 2.84(2H, t, J=8 Hz), 5.60 (2H, s), 6.36 (1H, d, J=4.5 Hz), 6.91 (1H, d,J=4.5 Hz), 7.05 (1H, d, J=5 Hz), 7.30 (4H, s), 8.23 (1H, d, J=5 Hz)

(13)3-[4-(2-Bromo-5-cyano-1-pyrrolyl)-2-methoxy]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.92 (3H, t, J=7 Hz), 1.43 (2H, m), 1.77 (2H, m), 2.73(3H, s), 2.93 (2H, t, J=7 Hz), 3.96 (3H, s), 5.56 (2H, s), 6.37 (1H, d,J=4 Hz), 6.71-6.89 (3H, m), 6.92 (1H, d, J=4 Hz), 7.07 (1H, d, J=5 Hz),8.23 (1H, d, J=5 Hz)

(14)2-Butyl-3-[4-(2-cyano-1-pyrrolyl)-3-nitrobenzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.96 (3H, t, J=7 Hz), 1.48 (3H, m), 1.83 (2H, m), 2.98(2H, t, J=7 Hz), 5.64 (2H, s), 6.39 (1H, dd, J=4 Hz, 3 Hz), 6.88 (1H,dd, J=3 Hz, 2 Hz), 7.01 (1H, dd, J=4 Hz, 2 Hz), 7.12 (1H, d, J=4 Hz),7.44-7.56 (2H, m), 7.98 (1H, s), 8.25 (1H, d, J=4 Hz)

(15)2-Butyl-3-[3-chloro-4-(2-cyano-1-pyrrolyl)benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.95 (3H, t, J=7 Hz), 1.46 (2H, m), 1.80 (2H, m), 2.73(3H, s), 2.90 (2H, t, J=7.5 Hz), 5.56 (2H, s), 6.36 (1H, dd, J=4 Hz, 3Hz), 6.93 (1H, dd, J=3 Hz, 1Hz), 6.99 (1H, dd, J=4 Hz, 1Hz), 7.08 (1H,d, J=5 Hz), 7.15 (1H, dd, J=8 Hz, 1Hz), 7.34 (1H, d, J=8 Hz), 7.35 (1H,d, J=1Hz), 8.23 (1H, d, J=5 Hz)

Preparation 24

To a stirred mixture of 1-(4-methylphenyl)pyrrole-2-carbonitrile (10 g),silica gel (46 g) and carbon tetrachloride (150 ml) was added dropwise asolution of tertbutyl hypochlorite (8.1 g) in carbon tetrachloride (15ml). After stirring for 1 hour at ambient temperature, the precipitatewas filtered off and the filtrate was evaporated in vacuo to give anoily residue which was crystallized from n-hexane. The crystals werefurther purified by silica gel column chromatography (SiO₂ 100 g,n-hexane-toluene=1:1) and subsequent crystallization from n-hexane togive colorless crystals (3.92 g) of4-chloro-1-(4-methylphenyl)pyrrole-2-carbonitrile.

mp: 72°-74° C.

NMR (CDCl₃, δ): 2.43 (3H, s), 6.89 (1H, d, J=2 Hz), 7.02 (1H, d, J=2Hz), 7.33 (4H, s)

Preparation 25

The following compound was obtained according to a similar manner tothat of Preparation 7.

1-(4-Bromomethylphenyl)-4-chloropyrrole-2-carbonitrile

mp: 95°-97° C.

NMR (CDCl₃, δ): 4.52 (2H, s), 6.92 (1H, d, J=1Hz), 7.03 (1H, d, J=1Hz),7.41 (2H, d, J=8 Hz), 7.54 (2H, d, J=8 Hz)

Preparation 26

The following compound was obtained according to a similar manner tothat of Preparation 9.

2-Butyl-3-[4-(4-chloro-2-cyano-1-pyrrolyl)benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 112°-113° C.

NMR (CDCl₃, δ): 0.92 (3H, t, J=7.5 Hz), 1.32-1.53 (2H, m), 1.66-1.87(2H, m), 2.72 (3H, s), 2.90 (2H, t, J=7.5 Hz), 5.57 (2H, s), 6.89 (1H,d, J=1.5 Hz), 6.99 (1H, d, J=1.5 Hz), 7.09 (1H, d, J=5.0 Hz), 7.28 (2H,d, J=9.0 Hz), 7.39 (2H, d, J=9.0 Hz), 8.24 (1H, d, J=5.0 Hz)

Preparation 27

To a suspension of sodium hydride (114 mg, 60% oil dispersion) indimethyl sulfoxide (5 ml) was added dropwise a solution of2-butyrylamino-4-methyl-3-nitropyridine (605 mg) in dimethyl sulfoxide(10 ml) at ambient temperature under nitrogen atmosphere. The mixturewas stirred at the same temperature for one hour and a solution of1-(4-bromomethylphenyl)-4-chloropyrrole-2-carbonitrile (800 ml) indimethyl sulfoxide (10 ml) was added therein. The reaction mixture wasstirred at ambient temperature for 2 hours and quenched with ice water.The separated oil was extracted twice with ethyl acetate. The combinedextracts were washed with water, dried, and concentrated in vacuo. Theresidue was purified by column chromatography on silica gel eluted byn-hexane/ethylacetate (2/1-1/1) to yield2-[N-butyryl-N-[4-(4-chloro-2-cyano-1-pyrrolyl)benzyl]amino]-4-methyl-3-nitropyridine(723 mg).

mp: 139°-141° C.

NMR (CDCl₃, δ): 0.90 (3H, t, J=7.5 Hz), 1.57-1.80 (2H, m), 1.98-2.20(2H, broad peak), 2.42 (3H, s), 4.40-5.35 (2H, broad peak), 6.91 (1H, d,J=1Hz), 7.04 (1H, d, J=1Hz), 7.10-7.65 (5H, m), 8.40-8.58 (1H, m)

Preparation 28

A mixture of2-[N-butyryl-N-[4-(4-chloro-2-cyano-1-pyrrolyl)benzyl]amino]-4-methyl-3-nitropyridine(700 mg), iron powder (894 mg), acetic acid (1.8 ml) and ethanol (15 ml)was stirred under reflux for 15 hours. After being cooled to roomtemperature, the reaction mixture was filtered and the filtrate wasevaporated in vacuo. The residue was partitioned into ethyl acetate (100ml) and saturated aqueous sodium hydrogencarbonate solution. The organiclayer was washed with water, dried over magnesium sulfate and evaporatedin vacuo. The residue was purified by a silica gel column chromatography(n-hexane-ethyl acetate =1:1) to give3-[4-(4-chloro-2-cyano-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine(565 mg) as a pale yellow powder.

NMR (CDCl₃, δ): 1.01 (3H, t, J=7.5 Hz), 1.70-1.94 (2H, m), 2.71 (3H, s),2.33 (2H, t, J=7.5 Hz), 5.56 (2H, s), 6.89 (1H, d, J=1Hz), 7.00 (1H, d,J=1Hz), 7.07 (1H, d, J=5 Hz), 7.25 (2H, d, J=8 Hz), 7.38 (2H, d, J=8Hz), 8.22 (1H, d, J=5 Hz)

Preparation 29

The following compounds were obtained according to a similar manner tothat of Preparation 13.

(1) 1-(2-Fluoro-4-methylphenyl)pyrrole

NMR (CDCl₃, δ): 2.38 (3H, s), 6.33 (2H, t, J=2.5 Hz), 6.96-7.08 (4H, m),7.28 (1H, t, J=8.0 Hz)

(2) 1-(3-Fluoro-4-methylphenyl)pyrrole

mp: 64°-67.5° C.

NMR (CDCl₃, δ): 2.28 (3H, d, J=1.0 Hz), 6.32 (2H, t, J=2.5 Hz), 7.04(2H, t, J=2.5 Hz), 7.01-7.12 (2H, m), 7.21 (1H, t, J=8.0 Hz)

(3) Ethyl 3-methyl-4-(1-pyrrolyl)benzoate

NMR (CDCl₃, δ): 1.40 (3H, t, J=7.5 Hz), 2.30 (3H, s), 4.40 (2H, q, J=7.5Hz), 6.30-6.38 (2H, m), 6.77-6.85 (2H, m), 7.30 (1H, d, J=8 Hz), 7.93(1H, dd), 8.00 (1H, d)

Preparation 30

The following compounds were obtained according to a similar manner tothat of Preparation 3.

(1) 1-(3-Fluoro-4-methylphenyl)pyrrole-2-carbaldehyde

NMR (CDCl₃, δ): 2.32 (3H, d, J=1.0 Hz), 6.40 (1H, dd, J=4.5 Hz, 3.0 Hz),6.99-7.11 (3H, m), 7.15 (1H, dd, J=4.5 Hz, 1.0 Hz), 7.26 (1H, t, J=8.0Hz), 9.57 (1H, s)

(2) 1-(2-Bromo-4-methylphenyl)pyrrole-2-carbaldehyde mp: 116°-119° C.

NMR (CDCl₃, δ): 2.42 (3H, s), 6.42 (1H, dd, J=4.0 Hz, 3.0 Hz), 6.91-6.97(1H, m), 7.12 (1H, dd, J=4.0 Hz, 1.0 Hz), 7.19-7.24 (2H, m), 7.52 (1H,s), 9.49 (1H, s)

Preparation 31

The following compounds were obtained according to a similar manner tothat of Preparation 16.

(1) 5-Bromo-1-(3-fluoro-4-methylphenyl)pyrrole-2-carbaldehyde

mp: 126°-138.5° C.

NMR (CDCl₃, δ): 2.38 (3H, d, J=1.5 Hz), 6.47 (1H, d, J=4.5 Hz), 6.97(2H, d, J=8.0 Hz), 7.08 (1H, d, J=4.5 Hz), 7.31 (1H, t, J=8.0 Hz), 9.32(1H, s)

(2) 5-Bromo-1-(2-bromo-4-methylphenyl)pyrrole-2-carbaldehyde mp:110.5°-113.5° C.

NMR (CDCl₃, δ): 2.44 (3H, s), 6.51 (1H, d, J=4.5 Hz), 7.08 (1H, d, J=4.5Hz), 7.20-7.30 (2H, m), 7.54 (1H, d, J=0.5 Hz), 9.29 (1H, s)

Preparation 32

The following compounds were obtained according to a similar manner tothat of Preparation 19.

(1) 1-(4-Ethoxycarbonyl-2-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 1.44 (3H, t, J=7.5 Hz), 2.20 (3H, s), 4.42 (2H, q, J=7.5Hz), 6.35-6.43 (1H, m), 6.88-6.98 (1H, m), 6.98-7.04 (1H, m), 7.38 (1H,d, J=9 Hz), 8.00 (1H, dd, J=9 Hz, 1Hz), 8.07 (1H, d, J=1Hz)

(2) 1-(2-Fluoro-4-methylphenyl)pyrrole-2-carbonitrile

mp: 47°-52° C.

NMR (CDCl₃, ε): 2.41 (3H, s), 6.35 (1H, dd, J=4.5 Hz, 3.5 Hz), 6.94-7.15(4H, m), 7.31 (1H, t, J=8.0 Hz)

(3) 1-(4-Ethoxycarbonylphenyl)pyrrole-2-carbonitrile

mp: 110°-112° C.

NMR (CDCl₃, δ): 1.43 (3H, t, J=7.5 Hz), 4.43 (2H, q, J=7.5 Hz), 6.40(1H, q, J=4 Hz & 3 Hz), 7.05 (1H, q, J=4 Hz & 2 Hz), 7.16 (1H, q, J=3 Hz& 2 Hz), 7.57 (2H, d, J=10 Hz), 8.21 (2H, d, J=10 Hz)

Preparation 33

The following compounds were obtained according to a similar manner tothat of Preparation 4.

(1) 5-Bromo-1-(3-fluoro-4-methylphenyl)pyrrole-2-carbonitrile

mp: 56.5°-58° C.

NMR (CDCl₃, δ): 2.37 (3H, d, J=1.0 Hz), 6.38 (1H, d, J=4.5 Hz), 6.92(1H, d, J=4.5 Hz), 7.02-7.11 (2H, m), 7.35 (1H, t, J=8.0 Hz)

(2) 5-Bromo-1-(2-bromo-4-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.45 (3H, s), 6.39 (1H, d, J=4.5 Hz), 6.95 (1H, d, J=4.5Hz), 7.27 (2H, s), 7.59 (1H, s)

Preparation 34

The following compound was obtained according to a similar manner tothat of Preparation 2.

4-Bromo-1-(5-methyl-2-pyridyl)pyrrole-2-carbonitrile

mp: 97.5°-109.5° C.

NMR (CDCl₃, δ): 2.41 (3H, s), 7.01 (1H, d, J=1.5 Hz), 7.50 (1H, d, J=8.0Hz), 7.57 (1H, d, J=1.5 Hz), 7.70 (1H, dd, J=8.0 Hz, 1.0 Hz), 8.38 (1H,d, J=1.0 Hz)

Preparation 35

To a mixture of 1-(4-ethoxycarbonylphenyl)pyrrole-2-carbonitrile (5.16g) and aluminum chloride (5.72 g) in 1,2-dichloroethane (51 ml) wasadded a solution of dichloromethylmethyl ether (2.97 g) in1,2-dichloroethane (5 ml) in one portion at -15° C. The mixture wasstirred for one hour at the same temperature and thendichloromethylmethyl ether (0.6 g) was added therein. After stirring for3 hours at 5° C., the reaction mixture was quenched with 10%hydrochloric acid. The separated organic layer was washed with 10%hydrochloric acid three times, dried, and concentrated in vacuo. Theresidue was purified by flash column chromatography on silica gel elutedby 1% methanol in dichloromethane to yield1-(4-ethoxycarbonylphenyl)-4-formylpyrrole-2-carbonitrile (2.96 g) as apale yellow solid.

mp: 28°-129.5° C.

NMR (CDCl₃, δ): 1.46 (3H, t, J=7.5 Hz), 4.44 (2H, q, J=7.5 Hz), 7.48(1H, d, J=2 Hz), 7.59 (2H, d, J=10 Hz), 7.73 (1H, d, J=2 Hz), 8.27 (2H,t, J=10 Hz), 9.89 (1H, s)

Preparation 36

To a solution of dimethylsulfoxide (64 ml) was added sodium hydride (480mg, 60% oil dispersion) at ambient temperature. The suspension wasstirred at 60° C. for 50 minutes to give a clear solution. To the cooledsolution was added methyltriphenylphosphonium bromide (4.29 g) atambient temperature in one portion. The mixture was stirred at ambienttemperature for half an hour and at 50° C. for half an hour. The yellowmixture was cooled to ambient temperature and therein1-(4-ethoxycarbonylphenyl)-4-formylpyrrole-2-carbonitrile (2.68 g) wasadded in one portion. After stirring at ambient temperature for one andhalf hours, the mixture was quenched with aqueous hydrochloric acid andextracted with dichloromethane. The organic layer was washed withaqueous hydrochloric acid three times, dried, and concentrated in vacuo.The residue was purified by flash column chromatography on silica geleluted by 20% n-hexane in dichloromethane to yield1-(4-ethoxycarbonylphenyl)-4-vinylpyrrole-2-carbonitrile (1.80 g) as awhite solid.

mp: 118.5°-120° C.

NMR (CDCl₃, δ): 1.43 (3H, t, J=7.5 Hz), 4.42 (2H, q, J=7.5 Hz), 5.18(1H, d, J=10 Hz), 5.56 (1H, d, J=17.5 Hz), 6.56 (1H, q, J=10 Hz & 17.5Hz), 7.14 (2H, s), 7.56 (2H, d, J=7.5 Hz), 8.21 (2H, d, J=7.5 Hz)

Preparation 37

A mixture of 1-(4-ethoxycarbonylphenyl)-4-vinylpyrrole- 2-carbonitrile(1.59 g) and lithium borohydride (78.4 mg) in tetrahydrofuran (30 ml)was refluxed for 3 hours. To the pale green solution was added lithiumborohydride (78.4 mg) and the mixture was refluxed for 3 hours. Thecooled mixture was quenched with saturated aqueous ammonium chloridesolution and diethyl ether was added. The separated organic layer waswashed with saturated aqueous ammonium chloride solution, dried, andconcentrated in vacuo. The residue was purified by flash columnchromatography on silica gel eluted by 2% methanol in dichloromethane toyield 1-(4-hydroxymethylphenyl)-4-vinylpyrrole-2-carbonitrile (910 mg)as a white solid.

mp: 77°-79° C.

NMR (CDCl₃, δ): 4.79 (2H, s), 5.16 (1H, d, J=10 Hz), 5.54 (1H, d, J=17.5Hz), 6.55 (1H, q, J=10 Hz & 17.5 Hz), 7.10 (2H, s), 7.43 (2H, d, J=10Hz), 7.52 (2H, d, J=10 Hz)

Preparation 38

The following compound was obtained according to a similar manner tothat of Preparation 37.

1-(4-Hydroxymethyl-2-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 1.82 (1H, br), 2.14 (3H, s), 4.74 (2H, s), 6.30-6.40(1H, m), 6.85-6.93 (1H, m), 6 93-7.00 (1H, m), 7.22-7.40 (3H, m)

Preparation 39

To a mixture of 1-(4-methylphenyl)pyrrole-2-carbonitrile (546 mg) andaluminum chloride (532 mg) in dichloromethane (10 ml) was added t-butylchloride (368 mg) in dichloromethane (10 ml) in one portion at 5° C. Themixture was stirred at the same temperature for 20 minutes. The reactionmixture was quenched with 10% hydrochloric acid. The separated organiclayer was washed with 10% hydrochloric acid and water, successively,dried, and concentrated in vacuo. The residue was purified by flashcolumn chromatography on silica gel eluted by a mixture of ethyl acetateand n-hexane (1:6) to yield4-t-butyl-1-(4-methylphenyl)pyrrole-2-carbonitrile (660 mg).

mp: 77°-78° C.

NMR (CDCl₃, δ): 1.28 (9H, s), 2.40 (3H, s), 6.87 (1H, d, J=2 Hz), 6.90(1H, d, J=2 Hz), 7.27 (2H, d, J=10 Hz), 7.32 (2H, d, J=10 Hz)

Preparation 40

The following compounds were obtained according to a similar manner tothat of Preparation 7.

(1) 1-(4-Bromomethyl-2-fluorophenyl)pyrrole-2-carbonitrile

mp: 67°-69° C.

NMR (CDCl₃, δ): 4.50 (2H, s), 6.40 (1H, dd, J=4.5 Hz, 3.5 Hz), 6.99-7.10(2H, m), 7.28-7.51 (3H, m)

(2) 5-Bromo-1-(4-bromomethyl-3-fluorophenyl)pyrrole-2-carbonitrile

mp: 70.5°-73° C.

NMR (CDCl₃, δ): 4.57 (2H, s), 6.41 (1H, d, J=4.5 Hz), 6.95 (1H, d, J=4.5Hz), 7.15 (1H, dd, J=8.0 Hz, 1.0 Hz), 7.19 (1H, dd, J=8.0 Hz, 1.0 Hz),7.59 (1H, t, J=8.0 Hz)

(3) 4-Bromo-1-(5-bromomethyl-2-pyridyl)pyrrole-2-carbonitrile

mp: 107.5°-115° C.

NMR (CDCl₃, δ): 4.51 (2H, s), 7.03 (1H, d, J=1.0 Hz), 7.62 (1H, d, J=8.5Hz), 7.63 (1H, d, J=1.0 Hz), 7.93 (1H, dd, J=8.5 Hz, 1.5 Hz), 8.53 (1H,d, J=1.5 Hz)

(4) 5-Bromo-1-(2-bromo-4-bromomethylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 4.49 (2H, s), 6.42 (1H, d, J=4.0 Hz), 6.96 (1H, d, J=4.0Hz), 7.37 (1H, d, J=8.0 Hz), 7.53 (1H, dd, J=8.0 Hz, 1.5 Hz), 7.80 (1H,d, J=1.5 Hz)

(5) 1-(4-Bromomethylphenyl)pyrrole-2,5-dicarbonitrile

mp: 123°-138° C.

NMR (CDCl₃, δ): 4.53 (2H, s), 6.99 (2H, s), 7.46 (2H, d, J=8 Hz), 7.62(2H, d, J=8 Hz)

(6) 1-(4-Bromomethylphenyl)-4-tert-butylpyrrole-2-carbonitrile

mp: 108°-109° C.

NMR (CDCl₃, δ): 1.25 (9H, s), 4.52 (2H, s), 6.88 (1H, d, J=1Hz), 6.91(1H, d, J=1Hz), 7.36-7.56 (4H, m)

Preparation 41

To a solution of 1-(4-hydroxymethylphenyl)-4-vinylpyrrole-2-carbonitrile(910 mg) in dichloromethane (15 ml) was added pyridine (385 mg),4-dimethylaminopyridine (20 mg), methanesulfonyl chloride (560 mg)successively at 5° C. The mixture was stirred at ambient temperature for4 hours and then pyridine (385 mg) and methanesulfonyl chloride (560 mg)was added therein. The mixture was stirred at the same temperatureovernight, washed with aqueous hydrochloric acid, dried, andconcentrated in vacuo. The residue was purified by flash columnchromatography on silica gel eluted by dichloromethane to yield1-(4-chloromethylphenyl)-4-vinylpyrrole-2-carbonitrile (831 mg) as acolorless oil.

NMR (CDCl₃, δ): 4.64 (2H, s), 5.17 (1H, dd, J=1Hz & 10 Hz), 5.54 (1H,dd, J=1Hz & 17.5 Hz), 6.56 (1H, dd, J=10 Hz & 17.5 Hz), 7.10 (1H, d,J=1.5 Hz), 7.08 (1H, d, J=1.5 Hz), 7.44 (2H, d, J=7.5 Hz), 7.54 (2H, d,J=7.5 Hz)

Preparation 42

The following compound was obtained according to a similar manner tothat of Preparation 41.

1-(4-Chloromethyl-2-methylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.15 (3H, s), 4.60 (2H, s), 6.32-6.40 (1H, m), 6.85-6.93(1H, m), 6.93-7.01 (1H, m), 7.23-7.44 (3H, m)

Preparation 43

A mixture of ethyl 4-amino-3-nitrobenzoate (49.5 g) andN,N-dimethylaniline (90 ml) was heated at 110° C. under nitrogenatmosphere. To the solution was added valeryl chloride (29 ml) and themixture was stirred at 110° C. for 1.5 hours. After being cooled to roomtemperature, 1N hydrochloric acid was added until pH 2˜3 to the reactionmixture. The aqueous solution was extracted with ethyl acetate. Theorganic layer was separated and washed successively with water andbrine. The solution was dried over magnesium sulfate and the solvent wasevaporated in vacuo. The residue was purified with silica gel columnchromatography (ethyl acetate: n-hexane =1:5) to give ethyl3-nitro-4-valerylaminobenzoate (67.5 g).

NMR (CDCl₃, δ): 0.98 (3H, t, J=7.5 Hz), 1.35-1.56 (2H, m), 1.43 (3H, t,J=7.5 Hz), 1.67-1.85 (2H, m), 2.52 (2H, t, J=7.5 Hz), 4.43 (2H, q, J=7.5Hz), 7.82 (1H, dd, J=9.0 Hz, 1.0 Hz), 8.28 (1H, d, J=9.0 Hz), 9.41 (1H,d, J=1.0 Hz)

Preparation 44

The following compounds were obtained according to a similar manner tothat of Preparation 43.

(1) 6-Chloro-3-nitro-2-valerylaminopyridine

mp: 101°-102° C.

NMR (CDCl₃, δ): 0.96 (3H, t, J=7.5 Hz), 1.47 (2H, m), 1.72 (2H, m), 2.72(2H, t, J=7.5 Hz), 7.18 (1H, d, J=9 Hz), 8.43 (1H, d, J=9 Hz)

(2) 6-Methoxy-3-Nitro-2-valerylaminopyridine

mp: 62°-64° C.

NMR (CDCl₃, δ): 0.97 (3H, t, J=7.5 Hz), 1.43 (2H, m), 1.76 (2H, m), 2.79(2H, t, J=7.5 Hz), 4.06 (3H, s), 6.51 (1H, d, J=9 Hz), 8.42 (1H, d, J=9Hz)

Preparation 45

The following compounds were obtained according to a similar manner tothat of Preparation 27.

(1)4-Bromo-1-[4-[N-(5-ethoxycarbonyl-2-nitrophenyl)-N-valerylamino]methylphenyl]pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 0.87 (3H, t, J=7.5 Hz), 1.15-1.50 (5H, m), 1.54-1.80(2H, m), 1.99-2.18 (2H, m), 4.43 (2H, q, J=7.5 Hz), 4.63 (1H, d, J=15Hz), 5.20 (1H, d, J=15 Hz), 7.00 (1H, d, J=1Hz), 7.10 (1H, d, J=1Hz),7.30-7.40 (4H, m), 7.73 (1H, d, J=1Hz), 7.98 (1H, d, J=10 Hz), 8.21 (1H,dd, J=10 Hz, 1Hz)

(2)4-Bromo-1-[4-[N-(6-chloro-3-nitropyridin-2-yl)-N-valerylamino]methylphenyl}pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 0.87 (3H, t, J=7.5 Hz), 1.18-1.40 (2H, m), 1.52-1.76(2H, m), 2.28-2.55 (2H, m), 5.20-5.45 (2H, br), 6.98 (1H, d, J=1Hz),7.08 (1H, d, J=1Hz), 7.30-7.72 (5H, m), 8.23 (1H, d, J=8 Hz)

(3)4-Bromo-1-[4-[N-(6-methoxy-3-nitropyridin-2-yl)-N-valerylamino]methylphenyl]pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 0.85 (3H, t, J=7.5 Hz), 1.18-1.41 (2H, m), 1.50-1.75(4H, m), 2.05-2.48 (1H, br s), 5.10-5.45 (1H, br s), 6.65-6.86 (1H, m),6.95 (1H, d, J=1Hz), 7.06 (1H, d, J=1Hz), 7.20-7.60 (4H, m), 8.20-8.35(1H, m)

Preparation 46

To a solution of 3,4-diaminothiophene (156 mg) in ethanol (10 ml) wasadded trimethyl orthovalerate (0.29 ml) and pyridiniump-toluenesulfonate (4 mg). The mixture was refluxed for one hour andconcentrated in vacuo. The residue was purified by preparative thinlayer chromatography on silica gel developed by ethyl acetate to give2-butyl-1H-thieno[3,4-d]imidazole (155 mg) as crystals.

mp: 112°-114° C.

NMR (CDCl₃, δ): 0.92 (3H, t, J=7 Hz), 1.32-1.5 (2H, m), 1.7-1.9 (2H, m),2.79 (2H, t, J=7 Hz), 6.0-6.6 (1H, br s), 6.73 (2H, s)

Preparation 47

The following compounds were obtained according to a similar manner tothat of Preparation 9.

(1) 2-Butyl-3-[4-(2-cyano-1-pyrrolyl)-3-fluorobenzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 119°-122° C.

NMR (CDCl₃, δ): 0.92 (3H, t, J=7.5 Hz), 1.34-1.56 (2H, m), 1.70-1.89(2H, m), 2.72 (3H, s), 2.89 (2H, t, J=7.5 Hz), 5.54 (2H, s), 6.37 (1H,dd, J=4.5 Hz, 3.5 Hz), 6.95-7.14 (5H, m), 7.40 (1H, t, J=6.5 Hz), 8.23(1H, d, J=5 Hz)

(2)2-Butyl-3-[4-(5-bromo-2-cyano-1-pyrrolyl)-2-fluorobenzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.93 (3H, t, J=7.5 Hz), 1.33-1.56 (2H, m), 1.69-1.87(2H, m), 2.72 (3H, s), 2.93 (2H, t, J=7.5 Hz), 5.62 (2H, s), 6.39 (1H,d, J=4.5 Hz), 6.93 (1H, d, J=4.5 Hz), 7.01-7.17 (3H, m), 7.20 (1H, dd,J=10.0 Hz, 1.5 Hz), 8.26 (1H, d, J=5.0 Hz)

(3)3-[[2-(4-Bromo-2-cyano-1-pyrrolyl)pyridin-5-yl]methyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 135°-138.5° C.

NMR (CDCl₃, δ) 0.94 (3H, t, J=7.5 Hz), 1.33-1.55 (2H, m), 1.69-1.88 (2H,m), 2.70 (3H, s), 2.89 (2H, t, J=7.5 Hz), 5.53 (2H, s), 7.01 (1H, d,J=1.5 Hz), 7.08 (1H, d, J=5.0 Hz), 7.54 (1H, d, J=8.0 Hz), 7.56 (1H, d,J=1.5 Hz), 7.70 (1H, dd, J=8.0 Hz, 2.0 Hz), 8.22 (1H, d, J=5.0 Hz), 8.46(1H, d, J=2.0 Hz)

(4)3-[3-Bromo-4-(5-bromo-2-cyano-1-pyrrolyl)benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 139°-145.5° C.

NMR (CDCl₃, δ): 0.92 (3H, t, J=7.5 Hz), 1.31-1.54 (2H, m), 1.67-1.85(2H, m), 2.71 (3H, s), 2.89 (2H, t, J=7.5 Hz), 5.56 (2H, s), 6.39 (1H,d, J=4.0 Hz), 6.93 (1H, d, J=4.0 Hz), 7.09 (1H, d, J=5.0 Hz), 7.21 (1H,dd, J=7.5 Hz, 1.5 Hz), 7.31 (1H, d, J=7.5 Hz), 7.57 (1H, d, J=1.5 Hz),8.23 (1H, d, J=5.0 Hz)

(5)2-Butyl-3-[4-(2,5-dicyano-1-pyrrolyl)benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 159°-161° C.

NMR (CDCl₃, δ): 0.90 (3H, t, J=7.5 Hz), 1.28-1.52 (2H, m), 1.63-1.86(2H, m), 2.70 (3H, s), 2.86 (2H, t, J=7.5 Hz), 5.59 (2H, s), 6.96 (2H,s), 7.08 (1H, d, J=5 Hz), 7.33 (2H, d, J=8 Hz), 7.41 (2H, d, J=8 Hz),8.21 (1H, d, J=5 Hz)

(6)3-[4-(2-Cyano-1-pyrrolyl)-3-methylbenzyl]-7-methyl-3-propyl-3H-imidazo[4,5-b]pyridine

mp: 127°-128° C.

NMR (CDCl₃, δ): 1.03 (3H, t, J=7.5 Hz), 1.72-1.94 (2H, m), 2.08 (3H, s),2.72 (3H, s), 2.85 (3H, t, J=7.5 Hz), 5.52 (2H, s), 6.28-6.38 (1H, m),6.80-6.88 (1H, m), 6.91-6.99 (1H, m), 6.99-7.14 (3H, m), 7.20 (1H, d,J=8 Hz), 8.21 (1H, d, J=5 Hz)

(7)3-[4-(4-Bromo-2-cyano-1-pyrrolyl)benzyl]-2-butyl-3H-imidazo[4,5-d]pyrimidine

mp: 120°-125° C.

NMR (CDCl₃, δ): 0.94 (3H, t, J=7.5 Hz), 1.32-1.55 (2H, m), 1.75-1.95(2H, m), 2.92 (2H, t, J=7.5 Hz), 5.58 (2H, s), 6.99 (1H, d, J=1Hz), 7.08(1H, d, J=1Hz), 7.34 (2H, d, J=8 Hz), 7.44 (2H, d, J=8 Hz), 9.02 (1H,s), 9.12 (1H, s)

(8)2-Butyl-3-[4-(4-tert-butyl-2-cyano-1-pyrrolyl)benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.91 (3H, t, J=7.5 Hz), 1.26 (9H, s), 1.30-1.55 (2H, m),1.65-1.90 (2H, m), 2.73 (3H, s), 2.88 (2H, t), 5.54 (2H, s), 6.80 (1H,d, J=1Hz), 6.88 (1H, d, J=1Hz), 7.08 (1H, d, J=5 Hz), 7.23 (2H, d, J=8Hz), 7.39 (2H, d, J=8 Hz), 8.23 (1H, d, J=5 Hz)

(9)2-Butyl-3-[4-(4-chloro-2-cyano-1-pyrrolyl)benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.93 (3H, t, J=7.5 Hz), 1.30-1.53 (2H, m), 1.73-1.93(2H, m), 2.82 (2H, t, J=7.5 Hz), 5.57 (2H, s), 6.89 (1H, d, J=2 Hz),7.00 (1H, d, J=2 Hz), 7.19-7.46 (5H, m), 8.02 (1H, dd, J=8 Hz, 1Hz),8.36 (1H, dd, J=5 Hz, 1Hz)

(10)3-[4-(2-Cyano-4-vinyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.01 (3H, t, J=7.5 Hz), 1.70-1.92 (2H, m), 2.70 (3H, s),2.83 (2H, t, J=7.5 Hz), 5.14 (1H, dd, J=l1Hz, 1Hz), 5.43-5.60 (3H, m),6.52 (1H, dd, J=l1Hz, 17.5 Hz), 7.00-7.10 (3H, m), 7.25 (2H, d, J=8 Hz),7.39 (2H, d, J=8 Hz), 8.21 (1H, d, J=5 Hz)

(11)1-[4-(4-Bromo-2-cyano-1-pyrrolyl)benzyl]-2-butylthieno[3,4-d]imidazole

NMR (CDCl₃, δ): 0.88 (3H, t, J=7 Hz), 1.39 (2H, m), 1.78 (2H, m), 2.71(2H, t, J=7 Hz), 5.15 (2H, s), 6.24 (1H, d, J=2 Hz), 6.90 (1H, d, J=2Hz), 6.97 (1H, d, J=2 Hz), 7.00 (1H, d, J=2 Hz), 7.22 (2H, d, J=9 Hz),7.36 (2H, d, J=9 Hz)

(12)1-[4-(4-Bromo-2-cyano-1-pyrrolyl)benzyl]-2-butyl-4-chloro-5-hydroxymethylimidazole

mp: 154°-155° C.

NMR (CDCl₃, δ): 0.90 (3H, t, J=7 Hz), 1.36 (2H, m), 1.69 (2H, m), 2.60(2H, t, J=7 Hz), 4.52 (2H, s), 5.30 (2H, s), 6.98 (1H, d, J=2 Hz), 7.08(1H, d, J=2 Hz), 7.16 (2H, d, J=9 Hz), 7.42 (2H, d, J=9 Hz)

Preparation 48

The following compounds were obtained according to a similar manner tothat of Preparation 28.

(1)1-[4-(4-Bromo-2-cyano-1-pyrrolyl)benzyl]-2-butyl-6-ethoxycarbonyl-1H-benzimidazole

mp: 130°-132° C.

NMR (CDCl₃, δ): 0.94 (3H, t, J=7.5 Hz), 1.32-1.60 (5H, m), 1.76-1.99(2H, m), 2.93 (2H, t, J=7.5 Hz), 4.39 (2H, q, J=7.5 Hz), 5.50 (2H, s),6.98 (1H, d, J=1Hz), 7.08 (1H, d, J=1Hz), 7.20 (2H, d, J=8 Hz), 7.84(1H, d, J=8 Hz), 7.98-8.11 (2H, m)

(2)3-[4-(4-Bromo-2-cyano-1-pyrrolyl)benzyl]-2-butyl-5-chloro-3H-imidazo[4,5-b]pyridine

mp: 140°-141° C.

NMR (CDCl₃, δ): 0.98 (3H, t, J=7.5 Hz), 1.31-1.53 (2H, m), 1.70-1.92(2H, m), 2.88 (2H, t, J=7.5 Hz), 5.52 (2H, s), 6.98 (1H, d, J=1Hz), 7.06(1H, d, J=1Hz), 7.22-7.48 (5H, m), 8.04 (1H, d, J=8 Hz)

(3)3-[4-(4-Bromo-2-cyano-1-pyrrolyl)benzyl]-2-butyl-5-methoxy-3H-imiazo[4,5-b]pyridine

mp: 140°-143° C.

NMR (CDCl₃, δ): 0.92 (3H, t, J=7.5 Hz), 1.30-1.54 (2H, m), 1.70-1.90(2H, m), 2.82 (2H, t-like, J=7.5 Hz), 3.98 (3H, s), 5.48 (2H, s), 6.72(1H, d, J=10 Hz), 6.98 (1H, d, J=1Hz), 7.04 (1H, d, J=1Hz), 7.30-7.47(4H, m), 7.94 (1H, d, J=10 Hz)

Preparation 49

To a solution of 4-(4-methylphenyl)pyrrole-3-carbonitrile (2.0 g) in amixture of benzene (40 ml) and 50% aqueous sodium hydroxide solution (10ml) was added methyliodide (1.56 g) and tetrabutylammonium iodide (4.06g) in that order in an ice bath. The mixture was stirred for 3 hours atambient temperature and extracted twice with diethyl ether. The combinedorganic layers were washed with aqueous hydrochloric acid and thenwater, dried, and concentrated in vacuo to yield1-methyl-4-(4-methylphenyl)pyrrole-3-carbonitrile (2.03 g) as paleyellow crystals.

mp: 93°-94° C.

NMR (CDCl₃, δ): 2.38 (3H, s), 3.72 (3H, s), 6.78 (1H, d, J=2 Hz), 7.14(1H, d, J=2 Hz), 7.21 (2H, d, J=8 Hz), 7.52 (2H, d, J=8 Hz)

Preparation 50

A mixture of 1-methyl-4-(4-methylphenyl)pyrrole-3-carbonitrile (2.0 g),2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile (200 mg) andN-bromosuccinimide (1.91 g) in carbon tetrachloride (40 ml) was refluxedunder nitrogen atmosphere, cooled to ambient temperature, and filtered.The filtrate was washed with 5% sodium thiosulfate solution and water.The separated oil was extracted with carbon tetrachloride, dried, andevaporated under reduced pressure to give a mixture of2-bromo-1-methyl-3-(4-methylphenyl)pyrrole-4-carbonitrile and2-bromo-1-methyl-4-(4-methylphenyl)pyrrole-3-carbonitrile.

mp: 113°-115° C.

NMR (CDCl₃, δ): 2.39 (3H, s), 3.70 (3H, s), 7.20-7.35 (3H, m), 7.45 (2H,d, J=8 Hz)

Preparation 51

The following compound was obtained according to a similar manner tothat of Preparation 7.

A mixture of2-bromo-3-(4-bromomethylphenyl)-1-methylpyrrole-4-carbonitrile and2-bromo-4-(4-bromomethylphenyl)-1-methylpyrrole-3-carbonitrile

mp: 146°-149° C.

NMR (CDCl₃, δ): 3.69 (3H, s), 4.51 (2H, s), 7.35 (1H, s), 7.49-7.57 (4H,m)

Preparation 52

The following compound was obtained according to a similar manner tothat of Preparation 27.

A mixture of2-bromo-1-methyl-3-[4-[N-(4-methyl-3-nitropyridin-2-yl)-N-butyrylamino]methylphenyl]pyrrole-4-carbonitrileand2-bromo-1-methyl-4-[4-[N-(4-methyl-3-nitropyridin-2-yl)-N-butyrylamino]methylphenyl]pyrrole-3-carbonitrile.

NMR (CDCl₃, δ): 0.89 (3H, t, J=7.5 Hz), 1.55-1.85 (2H, m), 2.00-2.24(2H, br peak), 2.43 (3H, s), 3.70 (3H, s), 4.90-5.35 (2H, br peak),7.00-7.64 (6H, m), 8.37-8.52 (1H, m)

Preparation 53

The following compound was obtained according to a similar manner tothat of Preparation 28.

A mixture of3-[4-(2-bromo-4-cyano-1-methyl-3-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridineand3-[4-(2-bromo-3-cyano-1-methyl-4-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine.

mp: 105°-108° C.

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.5 Hz), 1.69-1.92 (2H, m), 2.70 (3H, s),3.69 (3H, s), 5.52 (2H, s), 7.02 (1H, d, J=5 Hz), 7.18 (2H, d, J=8 Hz),7.30 (1H, s), 7.48 (2H, d, J=8 Hz), 8.21 (1H, d, J=5 Hz)

Preparation 54

A solution of the mixture prepared by Preparation 53 (300 mg) inmethanol (15 ml) was hydrogenated over 10% palladium on carbon (300 mg)under a hydrogen atmosphere (3 atm) for 8 hours. The catalyst wasfiltered off and the filtrate was evaporated under reduced pressure. Theresidue was purified by preparative thin layer chromatography to give3-[4-(4-cyano-1-methyl-3-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine(117 mg) as crystals.

mp: 117°-120° C.

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.5 Hz), 1.69-1.91 (2H, m), 2.71 (3H, s),2.86 (2H, t, J=7.5 Hz), 3.71 (3H, s), 5.51 (2H, s), 6.76 (1H, d, J=2Hz), 7.06 (1H, d, J=5 Hz), 7.10-7.20 (3H, m), 7.53 (2H, d, J=9 Hz), 8.22(1H, d, J=5 Hz)

Preparation 55

To a solution of1-(4-ethoxycarbonylphenyl)-4-formylpyrrole-2-carbonitrile (2.0 g) in1,2-dichloroethane (10 ml) was added sodium borohydride (296 mg) in oneportion under nitrogen at ambient temperature. The mixture was stirredfor one hour at the same temperature and then quenched with aqueoussaturated ammonium chloride solution at 5° C. The organic layer waswashed with water and brine, dried, and concentrated in vacuo. Theresidue was purified by silica gel column chromatography eluted by amixture of ethyl acetate and n-hexane (2:1) to give1-(4-ethoxycarbonylphenyl)-4-hydroxymethylpyrrole-2-carbonitrile (1.3 g)as a white solid.

mp: 120°-121.5° C.

NMR (CDCl₃, δ): 1.43 (3H, t, J=7.0 Hz), 4.42 (2H, q, J=7.0 Hz), 4.65(2H, s), 7.04 (1H, d, J=1.0 Hz), 7.18 (1H, d, J=1.0 Hz), 7.55 (2H, d,J=9.0 Hz), 8.20 (2H, d, J=9.0 Hz)

Preparation 56

To a solution of1-(4-ethoxycarbonylphenyl)-4-hydroxymethylpyrrole-2-carbonitrile (500mg) in dichloromethane (5.5 ml) was added trifluoroacetic acid (2.8 ml)and triethylsilane (652 μl) in that order at 5° C. under nitrogen. Themixture was stirred at 5° C. for one and half hours and at ambienttemperature for one hour and then poured into a mixture of diethyl etherand n-hexane (1:1). The mixture was washed with saturated sodiumbicarbonate solution and brine, dried, and concentrated in vacuo. Theresidue was purified by column chromatography on silica gel (elution byethyl acetate/n-hexane=1/10) to yield1-(4-ethoxycarbonylphenyl)-4-methylpyrrole-2-carbonitrile (163 mg) as awhite solid.

mp: 72°-75.5° C.

NMR (CDCl₃, δ): 1.42 (3H, t, J=7.0 Hz), 2.16 (3H, s), 4.41 (2H, q, J=7.0Hz), 6.87 (1H, d, J=1.0 Hz), 6.93 (1H, d, J=1.0 Hz), 7.52 (2H, d, J=9.0Hz), 8.19 (2H, d, J=9.0 Hz)

Preparation 57

The following compound was obtained according to a similar manner tothat of Preparation 56.

1-(4-Ethoxycarbonylphenyl)-5-methylpyrrole-2-carbonitrile

mp: 99°-104° C.

NMR (CDCl₃, δ): 1.42 (3H, t, J=7.0 Hz), 2.18 (3H, s), 4.42 (2H, q, J=7.0Hz), 6.11 (1H, d, J=4.5 Hz), 6.90 (1H, d, J=4.5 Hz), 7.40 (2H, d, J=9.0Hz), 8.21 (2H, d, J=9.0 Hz)

Preparation 58

The following compounds were obtained according to a similar manner tothat of Preparation 37.

(1) 1-(4-Hydroxymethylphenyl)-4-methylpyrrole-2-carbonitrile

mp: 89°-95° C.

NMR (CDCl₃, δ): 1.76 (1H, br s), 2.16 (3H, s), 4.75 (2H, s), 6.81 (1H,d, J=1.0 Hz), 6.87 (1H, d, J=1.0 Hz), 7.41 (2H, d, J=9.0 Hz), 7.49 (2H,d, J=9.0 Hz)

(2) 1-(4-Hydroxymethylphenyl)-5-methylpyrrole-2-carbonitrile

NMR (CDCl₃, δ): 1.99 (1H, br), 2.15 (3H, s), 4.79 (2H, d, J=5.5 Hz),6.08 (1H, d, J=4.5 Hz), 6.87 (1H, d, J=4.5 Hz), 7.31 (2H, d, J=9.0 Hz),7.52 (2H, d, J=9.0 Hz)

(3) 3-Chloro-1-(4-hydroxymethylphenyl)-2-methylpyrrole-5-carbonitrile

NMR (CDCl₃, δ): 1.89 (1H, br s), 2.12 (3H, s), 4.80 (2H, s), 6.86 (1H,s), 7.29 (2H, d, J=9.0 Hz), 7.53 (2H, d, J=9.0 Hz)

Preparation 59

The following compound was obtained according to a similar manner tothat of Preparation 41.

1-(4-Chloromethylphenyl)-4-methylpyrrole-2-carbonitrile

mp: 115°-120° C.

NMR (CDCl₃, δ): 2.15 (3H, s), 4.63 (2H, s), 6.82 (1H, d, J=1.0 Hz), 6.88(1H, d, J=1.0 Hz), 7.42 (2H, d, J=9.0 Hz), 7.52 (2H, d, J=9.0 Hz)

Preparation 60

To a solution of1-(4-hydroxymethylphenyl)-5-methylpyrrole-2-carbonitrile (890 mg) indichloromethane (9 ml) was added triethylamine (794 μl) andmethanesulfonyl chloride (343 μl) at 0° C. under nitrogen atmosphere.The mixture was stirred at 0° C. for an hour and then dichloromethanewas added therein. The mixture was stirred and washed with water twiceand brine, dried over magnesium sulfate and concentrated in vacuo togive 1-(4-methanesulfonyloxymethylphenyl)-5-methylpyrrole-2-carbonitrile(1.19 g).

NMR (CDCl₃, δ): 2.18 (3H, s), 3.03 (3H, s), 5.31 (2H, s), 6.10 (1H, d,J=4.5 Hz), 6.89 (1H, d, J=4.5 Hz), 7.37 (2H, d, J=9.0 Hz), 7.59 (2H, d,J=9.0 Hz)

Preparation 61

The following compounds were obtained according to a similar manner tothat of Preparation 60.

(1)3-Chloro-1-(4-methanesulfonyloxymethylphenyl)-2-methylpyrrole-5-carbonitrile

NMR (CDCl₃, δ): 2.12 (3H, s), 3.04 (3H, s), 5.31 (2H, s), 6.87 (1H, s),7.37 (2H, d, J=9.0 Hz), 7.61 (2H, d, J=9.0 Hz)

(2)1-(4-Methanesulfonyloxymethylphenyl)-5-methylthiopyrrole-2-carbonitrile

mp: 95°-98° C.

NMR (CDCl₃, δ): 2.20 (3H, s), 2.94 (3H, s), 5.24 (2H, s), 6.24 (1H, d,J=5 Hz), 6.90 (1H, d, J=5 Hz), 7.38 (2H, d, J=8 Hz), 7.51 (2H, d, J=8Hz)

Preparation 62

The following compound was obtained according to a similar manner tothat of Preparation 27.

2-[N-Butyryl-N-[4-(2-cyano-4-methyl-1-pyrrolyl)benzyl]amino]-4-methyl-3-nitropyridine

NMR (CDCl₃, δ): 0.88 (3H, t, J=7.0 Hz), 1.56-1.80 (2H, m), 2.02-2.19(2H, m), 2.12 (3H, s), 2.43 (3H, s), 4.72-5.30 (2H, m), 6.78-6.91 (3H,m), 7.26-7.53 (4H, m), 8.46-8.57 (1H, m)

Preparation 63

The following compound was obtained according to a similar manner tothat of Preparation 28.

3-[4-(2-Cyano-4-methyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.01 (3H, t, J=7.5 Hz), 1.71-1.92 (2H, m), 2.11 (3H, s),2.70 (3H, s), 2.83 (2H, t, J=7.5 Hz), 5.54 (2H, s), 6.79 (2H, d, J=1.0Hz), 7.06 (1H, d, J=5.0 Hz), 7.23 (2H, d, J=9.0 Hz), 7.36 (2H, d, J=9.0Hz), 8.21 (1H, d, J=5.0 Hz)

Preparation 64

The following compound was obtained according to a similar manner tothat of Preparation 3.

1-(4-Ethoxycarbonylphenyl)pyrrole-2-carbaldehyde

mp: 66°-69° C.

NMR (CDCl₃, δ): 1.41 (3H, t, J=7.0 Hz), 4.41 (2H, q, J=7.0 Hz), 6.44(1H, dd, J=4.0 & 3.0 Hz), 7.11 (1H, dd, J=3.0 & 1.0 Hz), 7.19 (1H, dd,J=4.0 & 1.0 Hz), 7.41 (2H, d, J=9.0 Hz), 8.16 (2H, d, J=9.0 Hz), 9.60(1H, s)

Preparation 65

The following compound was obtained according to a similar manner tothat of Preparation 55.

1-(4-Ethoxycarbonylphenyl)-2-hydroxymethylpyrrole

NMR (CDCl₃, δ): 1.41 (3H, t, J=7.5 Hz), 4.40 (2H, q, J=7.5 Hz), 4.54(2H, s), 6.29 (1H, dd, J=4.0 & 3.0 Hz), 6.37 (1H, dd, J=4.0 & 1.0 Hz),6.92 (1H, dd, J=3.0 & 1.0 Hz), 7.60 (2H, d, J=9.0 Hz), 8.15 (2H, d,J=9.0 Hz)

Preparation 66

To a solution of 1-(4-ethoxycarbonylphenyl)-2-hydroxymethylpyrrole (8.97g) in dichloromethane (90 ml) was added triethylamine (12.1 ml),4-dimethylaminopyridine (100 mg) and tert-butylchlorodiphenylsilane(10.6 ml) in that order at 5° C. under nitrogen atmosphere. Afterstirring for half an hour at 5° C., the mixture was allowed to warm toambient temperature and stirred for 13.5 hours. The mixture was washedwith water and brine, dried, concentrated in vacuo. The residue waspurified by column chromatography on silica gel (elution by ethylacetate/n-hexane=1/7) to yield2-tert-butyldiphenylsilyloxymethyl-1-(4-ethoxycarbonylphenyl)pyrrole(18.67 g) as an oil.

NMR (CDCl₃, δ): 1.02 (9H, s), 1.44 (3H, t, J=7.5 Hz), 4.43 (2H, q, J=7.5Hz), 4.56 (2H, s), 6.13 (1H, dd, J=4.0 & 1.0 Hz), 6.23 (1H, dd, J=4.0 &3.5 Hz), 6.90 (1H, dd, J=3.5 & 1.0 Hz), 7.30-7.48 (6H, m), 7.59-7.76(6H, m), 8.12 (2H, d, J=9.0 Hz)

Preparation 67

The following compound was obtained according to a similar manner tothat of Preparation 19.

2-tert-Butyldiphenylsilyloxymethyl-1-[4-ethoxycarbonylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 0.98 (9H, s), 1.46 (3H, t, J=7.5 Hz), 4.43 (2H, q, J=7.5Hz), 4.45 (2H, s), 6.19 (1H, d, J=4.0 Hz), 6.91 (1H, d, J=4.0 Hz),7.29-7.59 (10H, m), 7.77 (2H, d, J=9.0 Hz), 8.16 (2H, d, J=9.0 Hz)

Preparation 68

To a solution of2-tert-butyldiphenylsilyloxymethyl-1-(4-ethoxycarbonylphenyl)pyrrole-2-carbonitrile(1.9 g) in tetrahydrofuran (19 ml) was added tetrabutylammonium fluoride(5.6 ml, 1M tetrahydrofuran solution) through syringe at ambienttemperature. The mixture was stirred for half an hour at the sametemperature and concentrated in vacuo. The residue was dissolved inethyl acetate and the solution was washed with aqueous hydrochloricacid, water and brine, and then dried, and concentrated in vacuo. Theoily residue was chromatographed on silica gel (elution by ethylacetate/n-hexane =1/1) to give1-(4-ethoxycarbonylphenyl)-5-hydroxymethylpyrrole-2-carbonitrile (702.5mg) as an oil.

NMR (CDCl₃, δ): 1.42 (3H, t, J=7.0 Hz), 4.44 (2H, q, J=7.0 Hz), 4.49(2H, s), 6.40 (1H, d, J=4.5 Hz), 6.97 (1H, d, J=4.5 Hz), 7.54 (2H, d,J=9.0 Hz), 8.23 (2H, d, J=9.0 Hz)

Preparation 69

The following compound was obtained according to a similar manner tothat of Preparation 68.

1-(4-Hydroxymethylphenyl)-5-methylthiopyrrole-2-carbonitrile

mp: 88°-91° C.

NMR (CDCl₃, δ): 2.28 (3H, s), 4.81 (2H, s), 6.30 (1H, d, J=5 Hz), 6.96(1H, d, J=5 Hz), 7.39 (2H, d, J=8 Hz), 7.53 (2H, d, J=8 Hz)

Preparation 70

The following compounds were obtained according to a similar manner tothat of Preparation 9.

(1)3-[4-(2-Cyano-5-methyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.0 Hz), 1.69-1.91 (2H, m), 2.10 (3H, s),2.72 (3H, s), 2.87 (2H, t, J=7.0 Hz), 5.57 (2H, s), 6.06 (1H, d, J=4.5Hz), 6.86 (1H, d, J=4.5 Hz), 7.08 (1H, d, J=5.0 Hz), 7.28 (4H, s), 8.23(1H, d, J=5.0 Hz)

(2)3-[4-(3-Chloro-5-cyano-2-methyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.5 Hz), 1.70-1.91 (2H, m), 2.08 (3H, s),2.71 (3H, s), 2.87 (2H, t, J=7.5 Hz), 5.57 (2H, s), 6.83 (1H, s), 7.08(1H, d, J=5.0 Hz), 7.23 (2H, d, J=9.0 Hz), 7.31 (2H, d, J=9.0 Hz), 8.23(1H, d, J=5.0 Hz)

(3)3-[4-(2-Cyano-5-methylthio-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.5 Hz), 1.68-1.90 (2H, m), 2.21 (3H, s),2.70 (3H, s), 2.82 (2H, t, J=7.5 Hz), 5.58 (2H, s), 6.28 (1H, d, J=5Hz), 6.91 (1H, d, J=5 Hz), 7.06 (1H, d, J=5 Hz), 7.22-7.48 (4H, m), 8.22(1H, d, J=5 Hz)

(4)2-Butyl-3-[4-[2-cyano-5-methyl-1-pyrrolyl)benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.91 (3H, t, J=7 Hz), 1.41 (2H, m), 1.75 (2H, m), 2.10(3H, s), 2.71 (3H, s), 2.87 (2H, t, J=7 Hz), 5.58 (2H, s), 6.05 (1H, d,J=4 Hz), 6.86 (1H, d, J=4 Hz), 7.07 (1H, d, J=5 Hz), 7.28 (4H, s), 8.23(1H, d, J=5 Hz)

(5)3-[4-(4-Chloro-2-cyano-1-pyrrolyl)benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.34 (3H, t, J=7.5 Hz), 2.61 (3H, s), 2.68 (3H, s), 2.87(2H, q, J=7.5 Hz), 5.53 (2H, s), 6.89 (1H, d, J=1Hz), 6.95 (1H, s), 7.00(1H, d, J=1Hz), 7.28 (2H, d, J=8 Hz), 7.38 (2H, d, J=8 Hz)

(6)3-[4-(2-Cyano-4-difluoromethyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.02 (3H, t, J=7.5 Hz), 1.72-1.98 (2H, m), 2.75 (3H, s),2.93 (2H, t, J=7.5 Hz), 5.59 (2H, s), 6.68 (1H, t, J=56 Hz), 7.05-7.18(2H, m), 7.18-7.37 (3H, m), 7.37-7.49 (2H, m), 8.29 (1H, d, J=5 Hz)

Preparation 71

To a suspension of1-(4-ethoxycarbonylphenyl)-5-methylpyrrole-2-carbonitrile (1.76 g) andsilica gel (8.0 g, Mallinckrodt) in tetrachloromethane (26 ml) was addeddropwise sulfuryl chloride (760 μl) at 5° C. under nitrogen atmosphere.The suspension was stirred at 5° C. for one hour and then at ambienttemperature for half an hour. The mixture was filtered off and washedwith a little amount of tetrachloromethane. The filtrate wasconcentrated in vacuo and the residue was purified by columnchromatography on silica gel (elution by ethyl acetate/n-hexane =1/7) toyield 4-chloro-1-(4-ethoxycarbonylphenyl)-5-methylpyrrole-2-carbonitrile(1.36 g)

mp: 101°-106° C.

NMR (CDCl₃, δ): 1.42 (3H, t, J=7.0 Hz), 2.15 (3H, s), 4.43 (2H, q, J=7.0Hz), 6.89 (1H, s), 7.38 (2H, d, J=9.0 Hz), 8.22 (2H, d, J=9.0 Hz)

Preparation 72

The following compound was obtained according to a similar manner tothat of Preparation 16.

5-Bromo-1-(4-tert-butyldiphenylsilyloxymethylphenyl)pyrrole-2-carbaldehyde

NMR (CDCl₃, δ): 1.12 (9H, s), 4.86 (2H, s), 6.49 (1H, d, J=4 Hz), 7.11(1H, d, J=4 Hz), 7.53-7.19 (10H, m), 7.78-7.67 (4H, m), 9.31 (1H, s)

Preparation 73

The following compound was obtained according to a similar manner tothat of Preparation 4.

5-Bromo-1-(4-tert-butyldiphenylsilyloxymethylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 1.13 (9H, s), 4.84 (2H, s), 6.37 (1H, d, J=4 Hz), 6.92(1H, d, J=4 Hz), 7.54-7.23 (10H, m), 7.76-7.66 (4H, m)

Preparation 74

To a mixture of N,N,N'-N'-tetramethylethylenediamine (1.55 ml) and5-bromo-1-(4-tert-butyldiphenylsilyloxymethylphenyl)pyrrole-2-carbonitrile(3.80 g) was added dropwise n-butyllithium solution (1.6M solution inn-hexane, 5.2 ml) during a period of 20 minutes at -60° C. undernitrogen atmosphere. The mixture was stirred for one hour at the sametemperature and then dimethyldisulfide (1 ml) was added therein in oneportion. The reaction mixture was allowed to warm to ambienttemperature, stirred overnight at the same temperature and then pouredinto ice water. The separated oil was extracted with ethyl acetate. Theorganic layer was washed with water, dried, and concentrated in vacuo togive the residue, which was purified by column chromatography on silicagel to yield1-(4-tert-butyldiphenylsilyloxymethylphenyl)-5-methylthiopyrrole-2-carbonitrile(1.94 g) as a solid.

mp: 145°-148° C.

NMR (CDCl₃, δ): 1.11 (9H, s), 2.27 (3H, s), 4.83 (2H, s), 6.30 (1H, d,J=5 Hz), 6.93 (1H, d, J=5 Hz), 7.29-7.53 (10H, m), 7.64-7.74 (4H, m)

Preparation 75

To a solution of diethylaminosulfur trifluoride (639 mg) indichloromethane (10 ml) was added4-formyl-1-(4-methylphenyl)pyrrole-2-carbonitrile (417 mg) in oneportion at ambient temperature. The mixture was stirred for 6.5 hours atthe same temperature and further more diethylaminosulfur trifluoride(0.5 ml) was added therein to complete the reaction. The mixture wasstirred overnight at the same temperature and then washed with water.The organic layer was dried and concentrated in vacuo to give an oilyresidue, which was purified by flash column chromatography on silica gel(elution by n-hexane/ethyl acetate =9/1) to yield4-difluoromethyl-1-(4-methylphenyl)pyrrole-2-carbonitrile (364 mg) as anyellow oil.

NMR (CDCl₃, δ): 2.43 (3H, s), 6.68 (1H, t, J=56 Hz), 7.09 (1H, br s),7.24 (1H, br s), 7.33 (4H, s)

Preparation 76

The following compound was obtained according to a similar manner tothat of Preparation 7.

1-(4-Bromomethylphenyl)-4-difluoromethylpyrrole-2-carbonitrile

mp: 74°-76° C.

NMR (CDCl₃, δ): 4.53 (2H, s), 6.79 (1H, t, J=56 Hz), 7.12 (1H, br s),7.28 (1H, br s), 7.45 (2H, d, J=10 Hz), 7.57 (2H, d, J=10 Hz)

Preparation 77

A mixture of 4-bromo-1-(4-methylphenyl)pyrrole-2-carbonitrile (3.66 g),sodium trifluoroacetate (7.62 g), cuprous iodide (5.34 g) andN-methylpyrrolidone (40 ml) was stirred at 200° C. under a nitrogenatmosphere for 11 hours. The mixture was filtered. The filtrate waspoured into water and extracted with ethyl acetate twice. The combinedorganic layer was dried over magnesium sulfate and evaporated in vacuo.The residue was purified by silica gel column chromatography to afford1-(4-methylphenyl)-4-trifluoromethylpyrrole-2-carbonitrile (0.98 g).

mp: 40°-42° C.

NMR (CDCl₃, δ): 2.44 (3H, s), 7.13 (1H, s like), 7.32 (5H, s)

Preparation 78

The following compound was obtained according to a similar manner tothat of Preparation 7.

1-(4-Bromomethylphenyl)-4-trifluoromethylpyrrole-2-carbonitrile

mp: 65°-68° C.

NMR (CDCl₃, δ): 4.53 (2H, s), 7.17 (1H, s like), 7.38 (1H, s like), 7.45(2H, d, J=9 Hz), 7.60 (2H, d, J=9 Hz)

Preparation 79

The following compound was obtained according to a similar manner tothat of Preparation 35.

1(4-Ethoxycarbonylphenyl)-5-formyl-4-methylpyrrole-2-carbonitrile

mp: 105°-108° C.

NMR (CDCl₃, δ): 1.42 (3H, t, J=7.5 Hz), 2.46 (3H, s), 4.43 (2H, q, J=7.5Hz), 6.82 (1H, s), 7.47 (2H, d, J=9.0 Hz), 8.23 (2H, d, J=9.0 Hz), 9.68(1H, s)

Preparation 80

The following compound was obtained according to similar manners tothose of Preparations 55 and 56, successively.

4,5-Dimethyl-1-[4-ethoxycarbonylphenyl)pyrrole-2-carbonitrile

mp: 58°-59° C.

NMR (CDCl₃, δ): 1.41 (3H, t, J=7.5 Hz), 2.09 (6H, s), 4.43 (2H, q, J=7.5Hz), 6.79 (1H, s), 7.40 (2H, d, J=9.0 Hz), 8.20 (2H, d, J=9.0 Hz)

Preparation 81

The following compound was obtained according to a similar manner tothat of Preparation 71.

5-Chloro-1-(4-ethoxycarbonylphenyl)-4-methylpyrrole-2carbonitrile

mp: 72°-75° C.

NMR (CDCl₃, δ): 1.42 (3H, t, J=7.5 Hz), 2.12 (3H, s), 4.42 (2H, q, J=7.5Hz), 6.83 (1H, s), 7.46 (2H, d, J=9.0 Hz), 8.21 (2H, d, J=9.0 Hz)

Preparation 82

The following compound was obtained according to a similar manner tothat of Preparation 16.

5-Bromo-1-(4-ethoxycarbonylphenyl)-4-methylpyrrole-2-carbonitrile

mp: 68°-70.5° C.

NMR (CDCl₃, δ): 1.42 (3H, t, J=7.5 Hz), 2.13 (3H, s), 4.43 (2H, q, J=7.5Hz), 6.86 (1H, s), 7.45 (2H, d, J=9.0 Hz), 8.21 (2H, d, J=9.0 Hz)

Preparation 83

The following compounds were obtained according to a similar manner tothat of Preparation 37.

(1) 4,5-Dimethyl-1-(4-hydroxymethylphenyl)pyrrole-2-carbonitrile

mp: 77.5°-82° C.

NMR (CDCl₃, δ): 2.05 (3H, s), 2.09 (3H, s), 4.74 (2H, s), 6.73 (1H, s),7.27 (2H, d, J=9.0 Hz), 7.49 (2H, d, J=9.0 Hz)

(2) 5-Chloro-1-(4-hydroxymethylphenyl)-4-methylpyrrole-2-carbonitrile

mp: 94°-99.5° C.

NMR (CDCl₃, δ): 1.85 (1H, t like), 2.11 (3H, s), 4.80 (2H, d, J=4.5 Hz),6.80 (1H, s), 7.35 (2H, d, J=9.0 Hz), 7.56 (2H, d, J=9.0 Hz)

(3) 5-Bromo-1-(4-hydroxymethylphenyl)-4-methylpyrrole-2-carbonitrile

mp: 84°-87.5° C.

NMR (CDCl₃, δ): 2.11 (3H, s), 4.80 (2H, s), 6.81 (1H, s), 7.32 (2H, d,J=9.0 Hz), 7.52 (2H, d, J=9.0 Hz)

Preparation 84

The following compounds were obtained according to a similar manner tothat of Preparation 60.

(1)4,5-Dimethyl-1-(4-methanesulfonyloxymethylphenyl)pyrrole-2-carbonitrile

mp: 91.5°-93.5° C.

NMR (CDCl₃, δ): 2.08 (6H, s), 3.01 (3H, s), 5.30 (2H, s), 6.75 (1H, s),7.35 (2H, d, J=9.0 Hz), 7.58 (2H, d, J=9.0 Hz)

(2)5-Chloro-1-(4-methanesulfonyloxymethylphenyl)-4-methylpyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.12 (3H, s), 3.02 (3H, s), 5.31 (2H, s), 6.81 (1H, s),7.42 (2H, d, J=9.0 Hz), 7.61 (2H, d, J=9.0 Hz)

(3)5-Bromo-1-(4-methanesulfonyloxymethylphenyl)-4-methylpyrrole-2-carbonitrile

NMR (CDCl₃, δ): 2.13 (3H, s), 3.01 (3H, s), 5.31 (2H, s), 6.84 (1H, s),7.40 (2H, d, J=9.0 Hz), 7.59 (2H, d, J=9.0 Hz)

(4)4-Ethoxycarbonyl-1-(4-methanesulfonyloxymethylphenyl)-2-(1-trityl-1H-tetrazol-5-yl)pyrrole

NMR (CDCl₃, δ): 1.37 (3H, t, J=8 Hz), 2.92 (3H, s), 4.32 (2H, q, J=8Hz), 5.19 (2H, s), 6.88-6.98 (6H, m), 7.18-7.39 (13H, m), 7.44 (1H, d,J=1.5 Hz), 7.55 (1H, d, J=1.5 Hz)

Preparation 85

To a solution of 2-butyrylamino-4,6-dimethyl-3-nitropyridine (2.49 g) indimethylformamide (12.5 ml) was added sodium hydride (441 mg) in anice-water bath. The mixture was stirred at room temperature for an hour,and a solution of1-(4-methanesulfonyloxymethylphenyl)-5-methylpyrrole-2-carbonitrile(3.05 g) in dimethylformamide (15 ml) was dropwise therein. The reactionmixture was stirred at room temperature for 5.5 hours and was stoodovernight. The separated oil was extracted with ethyl acetate. Theextract were washed with brine, dried, and concentrated in vacuo. Theresidue was purified by flash column chromatography eluted byn-hexane/ethyl acetate (1/1) to give2-[N-butyryl-N-[4-(2-cyano-5-methyl-1-pyrrolyl)benzyl]amino]-4,6-dimethyl-3-nitropyridine(2.75 g) as oil.

NMR (CDCl₃, δ): 0.89 (3H, t, J=7 Hz), 1.68 (2H, m), 2.10 (2H, m), 2.15(3H, s), 2.36 (3H, s), 2.52 (3H, s), 4.73-5.32 (2H), 6.06 (1H, d, J=4Hz), 6.86 (1H, d, J=4 Hz), 7.08-7.48 (5H)

Preparation 86

The following compounds were obtained according to a similar manner tothat of Preparation 85.

(1)2-[N-Butyryl-N-[4-(2-cyano-4,5-dimethyl-1-pyrrolyl)benzyl]amino]-4-methyl-3-nitropyridine

NMR (CDCl₃, δ): 0.88 (3H, t, J=7.5 Hz), 1.57-1.80 (2H, m), 1.98-2.20(2H, m), 2.04 (3H, s), 2.06 (3H, s), 2.42 (3H, s), 4.62-5.38 (2H, m),6.71

(1H, s), 7.07-7.55 (5H, m), 8.42-8.55 (1H, m)

(2)4,6-Dimethyl-2-[N-propionyl-N-[4-(2-cyano-5-methyl-1-pyrrolyl)benzyl]amino]-3-nitropyridine

NMR (CDCl₃, δ): 1.10 (3H, t, J=7 Hz), 2.13 (3H, s), 2.13-2 25 (2H, m),2.36 (3H, s), 2.52 (3H, s), 4.66-5.40 (2H, m), 6.04 (1H, m), 6.83 (1H,m), 7.03-7.75 (5H, m)

Preparation 87

The following compounds were obtained according to a similar manner tothat of Preparation 9.

(1)3-[4-(2-Cyano-4-trifluoromethyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.02 (3H, t, J=7 Hz), 1.83 (2H, dt, J-7 Hz, 7 Hz), 2.71(3H, s), 2.86 (2H, t, J=7 Hz), 5.58 (2H, s), 7.08 (1H, d, J=5 Hz), 7.15(1H, s like), 7.30 (2H, d, J=7 Hz), 7.32 (1H, s like), 7.40 (2H, d, J=7Hz), 8.22 (1H, d, J=5 Hz)

(2)3-[4-(4-Chloro-2-cyano-1-pyrrolyl)benzyl]-2-ethyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.42 (3H, t, J=7.5 Hz), 2.75 (3H, s), 2.92 (2H, q, J=7.5Hz), 5.58 (2H, s), 6.91 (1H, d, J=2 Hz), 7.01 (1H, d, J=2 Hz), 7.09 (1H,d, J=5 Hz), 7.31 (2H, d, J=9 Hz), 7.40 (2H, d, J=9 Hz), 8.25 (1H, d, J=5Hz)

(3)3-[4-(4-Chloro-2-cyano-1-pyrrolyl)benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.03 (3H, t, J=7.5 Hz), 1.78-2.02 (2H, m), 2.84 (2H, t,J=7.5 Hz), 5.58 (2H, s), 6.90 (1H, d, J=1Hz), 7.00 (1H, d, J=1Hz),7.20-7.45 (5H, m), 8.07 (1H, dd, J=8 Hz, 1Hz), 8.48 (1H, dd, J=5 Hz,1Hz)

(4)3-[4-(4-Chloro-2-cyano-1-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.99 (3H, s), 1.67-1.90 (2H, m), 2.60 (3H, s), 2.64 (3H,s), 2.77 (2H, t, J=7.5 Hz), 5.52 (2H, s), 6.89 (1H, d, J=1Hz), 6.93 (1H,s), 7.00 (1H, d, J=1Hz), 7.26 (2H, d, J=9 Hz), 7.37 (2H, d, J=9 Hz)

(5)3-[4-(5-Chloro-2-cyano-4-methyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.5 Hz), 1.69-1.90 (2H, m), 2.09 (3H, s),2.70 (3H, s), 2.82 (2H, t, J=7.5 Hz), 5.57 (2H, s), 6.77 (1H, s), 7.04(1H, d, J=5.0 Hz), 7.28 (4H, s), 8.21 (1H, d, J=5.0 Hz)

(6)3-[4-(5-Bromo-2-cyano-4-methyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 106°-109° C.

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.5 Hz), 1.69-1.90 (2H, m), 2.10 (3H, s),2.71 (3H, s), 2.85 (2H, t, J=7.5 Hz), 5.58 (2H, s), 6.80 (1H, s), 7.07(1H, d, J=5.0 Hz), 7.28 (4H, s), 8.23 (1H, d, J=5.0 Hz)

(7)3-[4-(2-Chloro-4-cyano-1-methyl-3-pyrrolyl]benzyl]-2-propyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ) 1.00 (3H, t, J=7.5 Hz), 1.69-1.91 (2H, m), 2.69 (3H, s),2.83 (2H, t, J=7.5 Hz), 3.67 (3H, s), 5.52 (2H, s), 7.03 (1H, d, J=5Hz), 7.13-7.24 (3H, m), 7.51 (2H, d, J=9 Hz), 8.21 (1H, d, J=5 Hz)

Preparation 88

The following compounds were obtained according to a similar manner tothat of Preparation 28.

(1)3-[4-(2-Cyano-5-methyl-1-pyrrolyl)benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 182°-183.5° C.

NMR (CDCl₃, δ): 1.34 (3H, t, J=8 Hz), 2.09 (3H, s), 2.60 (3H, s), 2.65(3H, s), 2.84 (2H, q, J=8 Hz), 5.53 (2H, s), 6.04 (1H, d, J=5 Hz), 6.85(1H, d, J=5 Hz), 6.92 (1H, s), 7.22 (2H, d, J=7 Hz), 7.26 (2H, d, J=7Hz)

(2)3-[4-(2-Cyano-4,5-dimethyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imiazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.99 (3H, t, J=7.5 Hz), 1.70-1.92 (2H, m), 2.00 (3H, s),2.04 (3H, s), 2.70 (3H, s), 2.87 (2H, t, J=7.5 Hz), 5.57 (2H, s), 6.71(1H, s), 7.06 (1H, d, J=5.0 Hz), 7.21 (2H, d, J=9.0 Hz), 7.28 (2H, d,J=9.0 Hz), 8.23 (1H, d, J=5.0 Hz)

(3)3-[4-(2-Cyano-5-methyl-1-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.97 (3H, t J=7 Hz) 1.76 (2H dt J=7 Hz, 7 Hz), 2.61 (3H,s), 2.65 (3H, s), 2.78 (2H, t, J=7 Hz), 5.53 (2H, s), 6.06 (1H, d, J=4Hz), 6.86 (1H, d, J=4 Hz), 6.92 (1H, s), 7.28 (4H, s)

Preparation 89

The following compound was obtained according to a similar manner tothat of Preparation 4.

1-(4-tert-Butyldiphenylsilyloxymethylphenyl)pyrrole-2-carbonitrile

NMR (CDCl₃, δ): 1.11 (9H, s), 4.82 (2H, s), 6.35 (1H, dd, J=5 Hz, 4 Hz),6.99 (1H, dd, J=5 Hz, 2 Hz), 7.08 (1H, dd, J=4 Hz, 2 Hz), 7.30-7.53(10H, m), 7.62-7.74 (4H, m)

Preparation 90

The following compound was obtained according to a similar manner tothat of Preparation 1.

4-Bromo-1-(4-tert-butyldiphenylsilyloxymethylphenyl)pyrrole-2-carbonitrile

mp: 88°-90° C.

NMR (CDCl₃, δ): 1.10 (9H, s), 4.81 (2H, s), 6.97 (1H, d, J=2 Hz), 7.09(1H, d, J=2 Hz), 7.32-7.58 (10H, m), 7.65-7.80 (2H, m)

Preparation 91

A mixture of4-bromo-1-(4-tert-butyldiphenylsilyloxymethylphenyl)pyrrole-2-carbonitrile(2.02 g) and trimethyltin azide (2.42 g) in xylene (20 ml) was stirredat 120° C. for 14 hours. After cooled to ambient temperature, thereaction mixture was concentrated in vacuo. To the residue was addedtrityl chloride (42 mg), triethylamine (50 μl) and methylene chloride (1ml), and the mixture was treated in a conventional manner to give4-bromo-1-(4-tert-butyldiphenylsilyloxymethylphenyl)-2-(1-trityl-1H-tetrazol-5-yl)pyrrole(1.63 g)

NMR (CDCl₃, δ): 1.12 (9H, s), 4.73 (2H, s), 6.84-7.51 (27H, m),7.64-7.76 (4H, m)

Preparation 92

To a stirred solution of4-bromo-1-(4-tert-butyldiphenylsilyloxymethylphenyl)-2-(1-trityl-1H-tetrazol-5-yl)pyrrole(500 mg) in a mixture of tetrahydrofuran (5 ml) andN,N,N',N'-tetramethylethylenediamine (0.19 ml) was added n-butyl lithium(0.41 ml; 1.6M in n-hexane) at -78° C. under nitrogen atmosphere and themixture was stirred at the same temperature for half an hour. Ethylchloroformate (0.3 ml) was added to the mixture at the same temperatureand the resulting mixture was stirred at -78° C. for half an hour, at 0°C. for one hour and then at ambient temperature for two hours. Thereaction was quenched with aqueous saturated sodium bicarbonate anddiluted with ethyl acetate. The organic layer was washed with brine anddried over magnesium sulfate. After filtration, the filtrate wasconcentrated and the residue was purified by flash chromatography elutedwith a mixture of ethyl acetate-n-hexane 1:9 (V/V) to give1-(4-tert-butyldiphenylsilyloxymethylphenyl)-4-ethoxycarbonyl-2-(1-trityl-1H-tetrazol-5-yl)pyrrole(311 mg) as a colorless viscous oil.

NMR (CDCl₃, δ): 1.12 (9H, s), 1.36 (3H, t, J=8 Hz), 4.31 (2H, q, J=8Hz), 4.72 (2H, s), 6.83-6.98 (4H, m), 7.09-7.46 (20H, m), 7.55 (1H, d,J=1Hz), 7.64-7.75 (4H, m)

Preparation 93

The following compound was obtained according to a similar manner tothat of Preparation 68.

4-Ethoxycarbonyl-1-(4-hydroxymethylphenyl)-2-(1-trityl-1H-tetrazol-5-yl)pyrrole

NMR (CDCl₃, δ): 1.36 (3H, t, J=8 Hz), 4.31 (2H, q, J=8 Hz), 4.67 (2H, brd, J=4 Hz), 6.85-7.02 (13H, m), 7.13-7.39 (6H, m), 7.43 (1H, d, J=2 Hz),7.55 (1H, d, J=5 Hz)

Preparation 94

To a stirred solution of diethyl cyanomethylphosphonate (96 ml) in1,2-dimethoxyethane (375 ml) was added sodium hydride (60%: 22g)portionwise below 5° C. and the stirring was continued at 0° C. for halfan hour and then at ambient temperature for half an hour. The reactionmixture was recooled to 0° C. and a solution of methyl p-formylbenzoate(75 g) in 1,2-dimethoxyethane (375 ml) was added to the reaction mixturebelow 6° C. The reaction mixture was quenched with saturated aqueoussodium bicarbonate and diluted with ethyl acetate. The organic layer waswashed with water and aqueous saturated sodium bicarbonate and driedover magnesium sulfate and filtered. The solvent was removed in vacuoand the solid product was recrystallized from ethanol to give4-methoxycarbonylcinnamonitrile (52.12 g) as a white needle.

mp: 141°-144° C.

NMR (CDCl₃, δ): 3.95 (3H, s), 6.00 (1H, d, J=17 Hz), 7.45 (1H, d, J=17Hz), 7.53 (2H, d, J=9 Hz), 8.09 (2H, d, J=9 Hz)

Preparation 95

(4-Methoxycarbonylphenyl)-1H-pyrrole-3-carbonitrile (13.21 g) wasprepared by reacting 4-methoxycarbonylcinnamonitrile (50 g) withp-tolylmethyl isocyanide (62.5 g) in a conventional manner.

mp: 171°-172° C.

NMR (CDCl₃, +CD₃ OD, δ): 3.93 (3H, s), 7.04-7.11 (1H, m), 7.35-7.41 (1H,m), 7.73 (2H, d, J=9 Hz), 8.07 (2H, d, J=9 Hz)

Preparation 96

To a stirred solution of4-(4-methoxycarbonylphenyl)-1H-pyrrole-3-carbonitrile (3.00 g) inN,N-dimethylformamide (25 ml) was added sodium hydride 60% oildispersion: 559mg) at ambient temperature and the stirring was continuedfor half an hour at the same temperature. Iodomethane (1.99 g) was addedto the mixture, and was stirred at ambient temperature for two hours.The reaction mixture was poured onto ice water and extracted with ethylacetate and washed with 7% aqueous hydrochloric acid. The organic layerwas dried over magnesium sulfate, filtered and concentrated in vacuo.The residue was recrystallized from ethanol to give4-(4-methoxycarbonylphenyl)-1-methylpyrrole-3-carbonitrile (2.78 g) aspale yellow needles.

mp: 125°-126° C.

NMR (CDCl₃, δ): 3.75 (3H, s), 3.93 (3H, s), 6.91 (1H, d, J=2 Hz), 7.20(1H, d, J=2 Hz), 7.70 (2H, d, J=9 Hz), 8.06 (2H, d, J=9 Hz)

Preparation 97

The following compound was obtained by reacting4-(4-methoxycarbonylphenyl)-1-methylpyrrole-3-carbonitrile with thionylchloride, silica gel and carbon tetrachloride in a conventional manner.

A mixture of5-chloro-4-(4-methoxycarbonylphenyl)-1-methylpyrrole-3-carbonitrile and2,5-dichloro-4-(4-methoxycarbonylphenyl)-1-methylpyrrole-3-carbonitrile.

NMR (CDCl₃, δ): 3.70, 3.71, 3.95, 7.24, 7.60-7.72, 8.07-8.17

Preparation 98

The following compounds were obtained according to a similar manner tothat of Preparation 37.

(1) 5-Chloro-4-(4-hydroxymethylphenyl)-1-methylpyrrole-3-carbonitrile

mp: 153°-155° C.

NMR (CDCl₃, δ): 3.69 (3H, s), 4.73 (2H, s), 7.21 (1H, s), 7.46 (2H, d,J=9 Hz), 7.59 (2H, d, J=9 Hz)

(2)2,5-Dichloro-4-(4-hydroxymethylphenyl)-1-methylpyrrole-3-carbonitrile

mp: 167°-170° C.

NMR (CDCl₃, δ): 3.68 (3H, s), 4.74 (2H, s), 7.46 (2H, d, J=9 Hz), 7.56(2H, d, J=9 Hz)

Preparation 99

To a stirred solution of5-chloro-4-(4-hydroxymethylphenyl)-1-methylpyrrole-3-carbonitrile (450mg) in methylene chloride (20 ml) was added triphenylphosphine (1.44 g)and carbon tetrabromide (1.21 g) successively at 0° C. and the resultingyellow solution was stirred at the same temperature for a while. Themixture was washed with aqueous saturated sodium bicarbonate and water,dried over magnesium sulfate and filtered. The organic layer wasconcentrated in vacuo and the residue was purified by flashchromatography eluted with a mixture of ethyl acetate and n-hexane 1:4(V/V) then with 1:3 (V/V) to give4-(4-bromomethylphenyl)-5-chloro-1-methylpyrrole-3-carbonitrile (220 mg)as a white solid.

mp: 128°-133° C.

NMR (CDCl₃, δ): 3.70 (3H, s), 4.63 (2H, s), 7.22 (1H, s), 7.49 (2H, d,J=9 Hz), 7.59 (2H, d, J=9 Hz)

Preparation 100

To a stirred suspension of 2-formylamino-2-(4-methylphenyl)acetic acid(4.00 g) in acetic anhydride (45 ml) was added 2-chloroacrylonitrile(16.5 ml) at room temperature and the resulting suspension was heated at90° C. for 2.5 hours. After cooling, the solvent was evaporated and theresidue was washed with isopropyl ether. The mixture was filtered andthe resulting solid was dissolved into ethyl acetate and the solutionwas washed with aqueous saturated sodium bicarbonate and watersuccessively. The organic layer was dried with magnesium sulfate,filtered and concentrated in vacuo. The residue was purified by silicagel column chromatography eluted with n-hexane/methylene chloride 1:3(V/V) to give 2-(4-methylphenyl)pyrrole-3-carbonitrile (0.73 g) as acolorless viscous oil.

NMR (CDCl₃, δ): 2.40 (3H, s), 6.50-6.58 (1H, m), 6.75-6.84 (1H, m), 7.27(2H, d, J=9 Hz), 7.59 (2H, d, J=9 Hz), 8.68 (1H, br s)

Preparation 101

The following compound was obtained according to a similar manner tothat of Preparation 96.

1-Ethyl-2-(4-methylphenyl)pyrrole-3-carbonitrile

NMR (CDCl₃, δ): 1.31 (3H, t, J=7 Hz), 2.40 (3H, s), 3.90 (2H, q, J=7Hz), 6.47 (1H, d, J=4 Hz), 6.70 (1H, d, J=4 Hz), 7.28 (5H, s)

Preparation 102

The following compound was obtained according to a similar manner tothat of Preparation 1.

A mixture of 5-bromo-1-ethyl-2-(4-methylphenyl)pyrrole-3-carbonitrileand 4-bromo-1-ethyl-2-(4-methylphenyl)pyrrole-3-carbonitrile.

NMR (CDCl₃, δ): 1.23 (3H, t, J=7 Hz), 2.42 (3H, s), 3.95 (2H, q, J=7Hz), 6.51 (0.63H, s), 7.28 (4.37H, s)

Preparation 103

The following compound was obtained according to a similar manner tothat of Preparation 7.

A mixture of5-bromo-2-(4-bromomethylphenyl)-1-ethylpyrrole-3-carbonitrile and4-bromo-2-(4-bromomethylphenyl)-1-ethylpyrrole-3-carbonitrile

(This compound was used to the next reaction without furthermorepurification.)

Preparation 104

The following compounds were obtained according to a similar manner tothat of Preparation 9.

(1) A mixture of3-[4-(5-bromo-3-cyano-1-ethyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridineand3-[4-(4-bromo-3-cyano-1-ethyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.00 (3H, t, J=7 Hz), 1.19 and 1.20 (total 3H, each t,J=7 Hz), 1.81 (2H, m), 2.75 (3H, s), 2.91 (2H, m), 3.90 (2H, q, J=7 Hz),5.58 (2H, s), 6.50 (0.6H, s), 7.10 (1H, d, J=5 Hz), 7.28 (2H, d, J=8Hz), 7.85 (2H, d, J=8 Hz), 8.24 and 8.26 (total 1H, each d, J=5 Hz)-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.02 (3H, t, J=8 Hz), 1.20 (3H, t, J=7 Hz), 1.83 (2H,m), 2.73 (3H, s), 2.90 (2H, dd, J=8 Hz, 7 Hz), 3.90 (2H, d, J=7 Hz),5.58 (2H, s), 6.51 (1H, s), 7.09 (1H, d, J=4 Hz), 7.25 (2H, d, J=8 Hz),7.35 (2H, d, J=8 Hz), 8.25 (1H, d, J=4 Hz)

Preparation 105

A mixture of3-[4-(5-bromo-3-cyano-1-ethyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridineand3-[4-(4-bromo-3-cyano-1-ethyl-2-pyrroloyl)benzyl]-7-methyl-2-propyl-3H-imiazo[4,5-b]pyridinewas dissolved in methanol (15 ml) and hydrogenated with 10% palladium oncharcoal (300 mg) and potassium hydroxide (180 mg) at atmosphericpressure at ambient temperature for two hours. Concentrated hydrochloricacid was added until the pH of the solution was adjusted to 1 and thentriethylamine was added until the pH was alkaline. The mixture wasfiltered through celite and the filtrate was concentrated in vacuo. Theresidue was chromatographed on silica gel eluted with ethyl acetate togive3-[4-(3-cyano-1-ethyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridineas a colorless oil.

NMR (CDCl₃, δ): 1.01 (3H, t, J=7.0 Hz), 1.28 (3H, t, J=8 Hz), 1.82 (2H,m), 2.73 (3H, s), 2.91 (2H, t, J=7 Hz), 3.86 (2H, q, J=8 Hz), 5.58 (2H,s), 6.50 (1H, d, J=2 Hz), 6.70 (1H, d, J=2 Hz), 7.09 (1H, d, J=4 Hz),7.24 (2H, d, J=8 Hz), 7.35 (2H, d, J=8 Hz), 8.25 (1H, d, J=4 Hz)

Preparation 106

To a solution of 4-bromotoluene (1.42 g) in dry tetrahydrofuran (15 ml)was added n-butyl lithium solution (1.6 M in n-hexane, 5.2 ml) through asyringe at -78° C. under nitrogen atmosphere. The solution was stirredfor one hour at -78° C. and a solution of zinc chloride (1.130 in drytetrahydrofuran (10 ml) was added dropwise through a cannula therein atthe same temperature under nitrogen atmosphere. After stirring for onehour at ambient temperature, the mixture was added to a solution oftetrakis (triphenylphosphine) palladium(0) (320 mg) in drytetrahydrofuran (10 ml) through a cannula at ambient temperature undernitrogen atmosphere. The reaction mixture was allowed to stand overnightat the same temperature and poured into aqueous 1N hydrochloric acid.The separated oil was extracted twice with ethyl acetate. The extractswere washed with water, dried, and concentrated in vacuo. The residuewas purified by column chromatography on silica gel (elution byn-hexane/ethyl acetate=6/1) to give3-(4-methylphenyl)furane-2-carbaldehyde (1.01 g) as a yellow oil.

NMR (CDCl₃, δ): 2.52 (3H, s), 6.72 (1H, d, J=2 Hz), 7.29 (2H, d, J=9Hz), 7.47 (2H, d, J=9 Hz), 7.69 (1H, d, J=2 Hz), 9.75 (1H, s)

Preparation 107

A mixture of 3-(4-methylphenyl)furane-2-carbaldehyde (1.0 g),hydroxylamine hydrochloride (560 mg), and sodium acetate (660 mg) in 60%aqueous ethanol (10 ml) was stirred for one and half hours at 65° C. Themixture was concentrated in vacuo. The residue was dissolved in amixture of ethyl acetate and aqueous sodium bicarbonate solution. Theorganic layer was washed with brine, dried, and concentrated in vacuo togive a yellow solid. A mixture of the solid and sodium acetate (56 mg)in acetic anhydride (10.5 ml) was refluxed for 5 hours and thenevaporated in vacuo. The residue was purified by column chromatographyon silica gel (elution by n-hexane/ethyl acetate=15/1) to yield3-(4-methylphenyl)furane-2-carbonitrile (884 mg) as a yellow oil.

NMR (CDCl₃, δ): 2.40 (3H, s), 6.78 (1H, d, J=2 Hz), 7.27 (2H, d, J=9Hz), 7.54-7.64 (3H, m)

Preparation 108

A mixture of 3-(4-methylphenyl)furane-2-carbonitrile (884 mg),N-bromosuccinimide (902 mg), and2,2'-azobis-4-methoxy-2,4-dimethylvaleronitrile (130 mg) indichloromethane (10 ml) was refluxed for 2 hours. The mixture was cooledto ambient temperature, washed with aqueous sodium bicarbonate solutionand water successively, dried, and concentrated in vacuo. The residuewas column chromatographed on silica gel (elution byn-hexane/dichloromethane=4/1) to give3-(4-bromethylphenyl)furane-2-carbonitrile (905 mg) as a powder.

NMR (CDCl₃, δ): 4.51 (2H, s), 6.80 (1H, d, J=2 Hz), 7.50 (2H, d, J=9Hz), 7.61 (1H, d, J=2 Hz), 7.69 (2H, d, J=9 Hz)

Preparation 109

A mixture of 2-amino-4-methyl-3-nitropyridine (5.0 g) andN,N-dimethylaniline (8.5 ml) was heated at 100° C. under nitrogenatmosphere. To the solution was added butyryl chloride (3.5 ml) and themixture was stirred at 100° C. for 5 hours. After being cooled to roomtemperature, ethyl acetate was added to the reaction mixture. Theorganic layer was separated and washed successively with water andbrine. The solution was dried over magnesium sulfate and the solvent wasevaporated in vacuo. The residue was washed with n-hexane to give2-butyrylamino-4-methyl-3-nitropyridine (7.0 g).

mp: 92.5°-99° C.

NMR (CDCl₃, δ): 1.01 (3H, t, J=7.5 Hz), 1.64-1.85 (2H, m), 2.43 (2H, t,J=7.5 Hz), 2.48 (3H, s), 7.10 (1H, d, J=5.0 Hz), 8.26 (1H, br s), 8.35(1H, d, J=5.0 Hz)

Preparation 110

A solution of 2-butyrylamino-4-methyl-3-nitropyridine (7.0 g) and ironpowder (17.5 g) in a mixture of acetic acid (14 ml) and ethanol (100 ml)was stirred at 90° C. for 3 hours under nitrogen atmosphere. After beingcooled to room temperature, the reaction mixture was filtered throughCelite and the filtrate was evaporated in vacuo. Ethyl acetate andsaturated aqueous sodium hydrogencarbonate were added to the residueuntil pH 7-8 and the resulting suspension was filtered through Celite.The organic layer of the filtrate was separated, washed with brine anddried over magnesium sulfate. The solvent was evaporated in vacuo andthe residue was purified with silica gel column chromatography(eluent:ethyl acetate) to give7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine (3.6 g).

mp: 108°-111° C.

NMR (CDCl₃ δ): 1.09 (3H, t, J=7.5 Hz), 1.09-2.12 (2H, m), 2.72 (3H, s),3.06 (2H, t, J=7.5 Hz), 7.07 (1H, d, J=5.0 Hz), 8.19 (1H, d, J=5.0 Hz)

Preparation 111

To a suspension of sodium hydride (150 mg, 60% oil dispersion) indimethylsulfoxide (10 ml) was added7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine (595 mg) in one portion atambient temperature under nitrogen atmosphere. The mixture was stirredfor one hour at the same temperature and then a solution of3-(4-bromomethyl)furan-2-carbonitrile (890 mg) in dimethylsulfoxide (10ml) as added dropwise to the mixture. After stirring for 3 hours atambient temperature, the mixture was poured into diluted hydrochloricacid. The separated oil was extracted four times with ethyl acetate. Thecombined organic layers were washed with water, dried, and concentratedin vacuo. The residue was purified by column chromatography on silicagel (elution by n-hexane/ethyl acetate=1/1) to yield3-[4-(2-cyano-3-furyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine(555 mg) as an amorphous solid.

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.5 Hz), 1.70-1.92 (2H, m), 2.70 (3H, s),2.82 (2H, t, J=7.5 Hz), 5.53 (2H, s), 6.73 (1H, d, J=1 Hz), 7.05 (1H, d,J=5 Hz), 7.22 (2H, d, J=9 Hz), 7.53-7.68 (3H, m), 8.22 (1H, d, J=5 Hz)

Preparation 112

A mixture of 2-hydroxy-4'-methylbenzophenone (18.3 g),chloroacetonitrile (7.87 g) and potassium carbonate (14.2 g) inN,N'-dimethylformamide (183 ml) was stirred at ambient temperature for 5hours and then poured into ice water. The separated oil was extractedwith dichloromethane (×2). The organic layer were washed with water(×3), dried and concentrated in vacuo. The residue was purified by flashcolumn chromatography on silica gel eluted with dichloromethane to give2-cyanomethoxy-4'-methylbenzophenone (21.3 g) as a yellow oil.

NMR (CDCl₃, δ): 2.42 (3H, s), 4.72 (2H, s), 7.10-7.72 (8H, m)

Preparation 113

To a solution of 2-(4-methylphenyl)benzo[b]thiophene (896 mg) in freshlydistillated tetrahydrofuran (15 ml) was added n-butyllithium (2.75 ml,1.6 mol solution in n-hexane) through a syringe at -78° C. The solutionwas stirred at -78° C. for 10 minutes and then at ambient temperaturefor half an hour. To the deep red colored solution was addedN,N-dimethylformamide (365mg) at 5° C. The mixture was stirred atambient temperature for one hour, quenched with aqueous saturatedammonium chloride solution, and extracted with diethyl ether. Theorganic layer was washed with aqueous saturated ammonium chloridesolution, dried, and concentrated in vacuo to give a yellow residue,which was purified by flash column chromatography on silica gel elutedwith 50% n-hexane in dichloromethane to yield2-(4-methylphenyl)benzo[b]thiophene-3-carbaldehyde (285 mg) as whitecrystals.

IR (Nujol): 1660 cm⁻¹

NMR (CDCl₃, δ): 2.50 (3H, s), 7.38 (2H, d, J=7.5 Hz), 7.45-7.60 (2H, m),7.54 (2H, d, J=7.5 Hz), 7.90 (1H, dd, J=2 Hz and 7.5 Hz), 8.82 (1H, dd,J=2 Hz and 7.5 Hz), 10.1 (1H, s)

Preparation 114

The following compounds were obtained according to a similar manner tothat of Preparation 3.

(1) 5-Chloro-3-(4-methylphenyl)thiophene-2-carbaldehyde

NMR (CDCl₃, δ): 2.43 (3H, s), 7.08 (1H, s), 7.28 (2H, d, J=8 Hz), 7.36(2H, d, J=8 Hz), 9.77 (1H, s)

(2) 2-(4-Methylphenyl)imidazo[1,2-a]pyridine-3-carbaldehyde

NMR (CDCl₃, δ): 2.44 (3H, s), 7.13 (1H, dt, J=7 Hz and 1 Hz), 7.34 (2H,d, J=7 Hz), 7.59 (1H, ddd, J=8 Hz, 7 Hz and 1 Hz), 7.74 (2H, d, J=7 Hz),7.83 (1H, dt, J=1 Hz and 8 Hz), 9.68 (1H, dd, J=7 Hz and 1 Hz), 10.07(1H, s)

(3) 2-(4-Methylphenyl)indolizine-3-carbaldehyde

NMR (CDCl₃, δ): 2.41 (3H, s), 6.58 (1H, s), 6.91 (1H, t, J=6 Hz), 7.23(1H, m), 7.26 (2H, d, J=8 Hz), 7.46 (2H, d, J=8 Hz), 7.55 (1H, d, J=8Hz), 9.75 (1H, s), 9.84 (1H, d, J=6 Hz)

Preparation 115

The following compound was obtained according to a similar manner tothat of the former half of Preparation 4.

2-(4-Methylphenyl)benzo[b]thiophene-3-carbaldehyde oxime

mp: 155°-157° C.

NMR (CDCl₃, δ): 2.44 (3H, s), 7.29 (2H, d, J=9.5 Hz), 7.42 (2H, d, J=9.5Hz), 7.34-7.50 (2H, m), 7.82 (1H, dd, J=2 Hz and 7.5 Hz), 8.35 (1H, s),8.59 (1H, dd, J=2 Hz and 7.5 Hz)

Preparation 116

The following compound was obtained according to a similar manner tothat of the latter half of Preparation 4.

2-(4-Methylphenyl)benzo[b]thiophene-3-carbonitrile

mp: 104°-106° C.

IR (Nujol): 2200 cm⁻¹

NMR (CDCl₃, δ): 2.45 (3H, s), 7.31 (2H, d, J=7.5 Hz), 7.39-7.54 (2H, m),7.79 (2H, d, J=7.5 Hz), 7.78-7.97 (2H, m)

Preparation 117

To a stirred solution of 2-picoline (5.12 g) in acetone (10 ml) wasadded 2-bromo-4'-methylacetophenone (10.4 g) in one portion and themixture was heated at 80° C. for one hour. After addition of diethylether, the crystalline product was collected and washed with diethylether. After drying in air for several hours, this product was suspendedin water (100 ml) and a solution of sodium bicarbonate (21 g) in water(100 ml) was added dropwise to the suspension. The mixture was stirredat ambient temperature for 45 minutes and refluxed for half an hour. Themixture was diluted with methylene chloride and washed with aqueoussaturated sodium chloride. The organic layer was separated, dried overpotassium carbonate and filtered. The solvent was removed in vacuo andthe resulting solid was recrystallized from benzene to give2-(4-methylphenyl)indolizine (7.51 g).

NMR (CDCl₃, δ): 2.36 (3H, s), 6.43 (1H, br t, J=6 Hz), 6.66 (2H, m),7.20 (2H, d, J=8 Hz), 7.32 (1H, d, J=8 Hz), 7.54 (2H, d, J=8 Hz), 7.52(1H, m), 7.89 (1H, br s)

Preparation 118

To a mixture of 2-cyanomethoxy-4'-methylbenzophenone (18.6 g) andmolecular sieves (18 g) in benzene (270 ml) was added potassiumtert-butoxide (8.31 g) in one portion at ambient temperature. Afterstirring at the same temperature for one hour, the mixture was filteredoff. The filtrate was washed with diluted hydrochloric acid, dried, andconcentrated in vacuo. The residue was purified by flash columnchromatography to yield 3-(4-methylphenyl)benzo[b]furan-2-carbonitrile(1.82 g) as white crystals.

mp: 131°-133.5° C.

IR (Nujol): 2200 cm⁻¹

Preparation 119

A mixture of 2-pyridyl acetonitrile (5.0 g) and2-bromo-4'-methylacetophenone (8.52 g) in acetone (10 ml) was heated at80° C. for 24 hours, during which 2-pyridylacetonitrile (1 g, 2 g) wasadded to the reaction mixture. After being cooled, the solvent wasremoved in vacuo and the residue was chromatographed on silica geleluted with a mixture of ethyl acetate and n-hexane (1:6 to 1:2, V/V) togive a solid product. This product was recrystallized from ethanol-waterto give 2-(4-methylphenyl)indolizine-1-carbonitrile (4.1 g) as a palebrown powder.

mp: 107°-109° C.

NMR (CDCl₃, δ): 2.40 (3H, s), 6.75 (1H, dd, J=7 Hz and 1 Hz), 7.06 (1H,ddd, J=1 Hz, 7 Hz and 8 Hz), 7.26 (2H, d, J=8 Hz), 7.42 (1H, s), 7.65(1H, m), 7.67 (2H, d, J=8 Hz), 8.00 (1H, br d, J=7 Hz)

Preparation 120

The following compounds were obtained according to a similar manner tothat of Preparation 4.

(1) 5-Chloro-3-(4-methylphenyl)thiophene-2-carbonitrile

NMR (CDCl₃, δ): 2.41 (3H, s), 7.13 (1H, s), 7.28 (2H, d, J=8 Hz), 7.55(2H, d, J=8 Hz)

(2) 2-(4-Methylphenyl)imidazo[1,2-a]pyridine-3-carbonitrile

NMR (CDCl₃, δ): 2.42 (3H, s), 7.09 (1H, dt, J=1 Hz and 7 Hz), 7.33 (2H,d, J=8 Hz), 7.46 (1H, ddd, J=1 Hz, 7 Hz and 8 Hz), 7.75 (1H, dd, J=1 Hzand 8 Hz), 8.09 (2H, d, J=8 Hz), 8.36 (1H, dd, J=1 Hz and 7 Hz)

(3) 2-(4-Methylphenyl)indolizine-3-carbonitrile

NMR (CDCl₃, δ): 2.40 (3H, s), 6.66 (1H, s), 6.81 (1H, dt, J=1 Hz and 7Hz), 7.02 (1H, dt, J=1 Hz and 7 Hz), 7.39 (2H, d, J=8 Hz), 7.49 (1H, d,J=7 Hz), 7.71 (2H, d, J=8 Hz), 8.26 (1H, d, J=7 Hz)

Preparation 121

The following compound was obtained according to a similar manner tothat of Preparation 35.

2-Formyl-3-(4-methoxycarbonylphenyl)-1-methylpyrrole-4-carbonitrile

mp: 197°-200° C.

NMR (CDCl₃, δ): 3.97 (3H, s), 4.05 (3H, s), 7.35 (1H, s), 7.56 (2H, d,J=9 Hz), 8.17 (2H, d, J=9 Hz), 9.61 (1H, s)

Preparation 122

The following compound was obtained according to similar manners tothose of Preparations 55 and 56, successively.

1,2-Dimethyl-3-(4-methoxycarbonylphenyl)pyrrole-4-carbonitrile

mp: 135°-138° C.

NMR (CDCl₃, δ): 2.29 (3H, s), 3.62 (3H, s), 3.93 (3H, s), 7.17 (1H, s),7.46 (2H, d, J=9 Hz), 8.10 (2H, d, J=9 Hz)

Preparation 123

The following compound was obtained according to a similar manner tothat of Preparation 37.

1,2-Dimethyl-3-(4-hydroxymethylphenyl)pyrrole-4-carbonitrile

NMR (CDCl₃, δ): 1.78 (1H, br s), 2.27 (3H, s), 3.61 (3H, s), 4.71 (2H,s), 7.13 (1H, s), 7.34-7.48 (4H, m)

Preparation 124

The following compound was obtained according to a similar manner tothat of Preparation 99.

3-(4-Chloromethylphenyl)-1,2-dimethylpyrrole-4-carbonitrile mp:170°-177° C.

NMR (CDCl₃, δ): 2.27 (3H, s), 3.62 (3H, s), 4.63 (2H, s), 7.14 (1H, s),7.34-7.50 (4H, m)

Preparation 125

The following compounds were obtained according to a similar manner tothat of Preparation 96.

(1) 2-(4-Methylphenyl)-1-propylpyrrole-3-carbonitrile

NMR (CDCl₃, δ): 0.80 (3H, t, J=8 Hz), 1.56 (2H, m), 2.40 (3H, s), 3.32(2H, t, J=8 Hz), 6.49 (1H, d, J=3 Hz), 6.69 (1H, d, J=3 Hz), 7.20-7.36(4H, m)

(2) 1-Isopropyl-2-(4-methylphenyl)pyrrole-3-carbonitrile

NMR (CDCl₃, δ): 1.37 (6H, d, J=7 Hz), 2.41 (3H, s), 4.40 (1H, m), 6.50(1H, d, J=4 Hz), 6.78 (1H, d, J=4 Hz), 7.28 (4H, s)

Preparation 126

The following compound was obtained according to similar manners tothose of Preparation 7 and 27, successively.

A mixture of4,6-dimethyl-3-nitro-2-[N-propionyl-N-[4-(4-bromo-3-cyano-1-ethyl-2-pyrrolyl)benzyl]amino]pyridineand4,6-dimethyl-3-nitro-2-[N-propionyl-N-[4-(5-bromo-3-cyano-1-ethyl-2-pyrrolyl)benzyl]amino]pyridine.

(This mixture was used to the next reaction without furtherpurification.)

Preparation 127

The following compound was obtained according to a similar manner tothat of Preparation 27.

4,6-Dimethyl-2-[N-propionyl-N-[4-(2-chloro-4-cyano-1-methyl-3-pyrrolyl)benzyl]amino]-3-nitropyridine

NMR (CDCl₃, δ): 1.11 (3H, t, J=7.5 Hz), 2.05-2.65 (8H, m), 3.68 (3H, s),4.55-5.40 (2H, br), 6.88-7.68 (6H, m)

Preparation 128

The following compounds were obtained according to a similar manner tothat of Preparation 50.

(1) 1-Bromo-2-(4-methylphenyl)indolizine-3-carbonitrile

NMR (CDCl₃, δ): 2.43 (3H, s), 6.88 (1H, dt, J=1 Hz and 7 Hz), 7.13 (1H,ddd, J=1 Hz, 7 Hz and 8 Hz), 7.30 (2H, d, J=8 Hz), 7.58 (1H, d, J=8 Hz),7.62 (2H, d, J=8 Hz), 8.27 (1H, d, J=7 Hz)

(2) 3-Bromo-2(4-methylphenyl)indolizine-1-carbonitrile

NMR (CDCl₃, δ): 2.42 (3H, s), 6.93 (1H, dt, J=0.5 and 7 Hz), 7.18 (1H,dt, J=0.5 Hz and 8 Hz), 7.32 (2H. d, J=7 Hz), 7.60 (2H, d. J=7 Hz1, 7.69(1H, d, J=8 Hz), 8.21 (1H, d, J=7 Hz)

Preparation 129

The following compounds were obtained according to a similar manner tothat of Preparation 1.

(1) A mixture of4-bromo-2-(4-methylphenyl)-1-propylpyrrole-3-carbonitrile and5-bromo-2-(4-methylphenyl)-1-propylpyrrole-3-carbonitrile (This mixturewas used to the next reaction without further purification.)

(2) 4,5-Dibromo-1-isopropyl-2-(4-methylphenyl)pyrrole-3-carbonitrile

(This compound was used to the next reaction without furtherpurification.)

Preparation 130

A mixture of 3-(4-methylphenyl)benzo[b]furan-2-carbonitrile (239 mg),N-bromosuccinimide (182 mg), and 2,2'-azobisisobutyronitrile (10 mg) incarbon tetrachloride (5 ml) was refluxed for 5 hours and cooled toambient temperature. The precipitates were filtered off. The filtratewas washed with aqueous sodium bicarbonate solution (×3), dried, andconcentrated in vacuo to give a yellow oil, which was crystallized fromn-hexane to yield 3-(4-bromomethylphenyl)benzo[b]furan-2-carbonitrile(300 mg) as a yellow solid.

NMR (CDCl₃, δ): 4.58 (2H, s), 7.38-7.88 (8H, m)

Preparation 131

The following compounds were obtained according to a similar manner tothat of Preparation 130.

(1) 2-(4-Bromomethylphenyl)benzo[b]thiophene-3-carbonitrile

NMR (CDCl₃, δ): 4.56 (2H, s), 7.30-8.04 (8H)

(2)3-(4-Bromomethylphenyl)-5-chloro-2-(1-trityl-1H-tetrazol-5-yl)thiophene

NMR (CDCl₃, δ): 4.48 (2H, s), 6.92-7.43 (20H)

(3)2-(4-Bromomethylphenyl)-3-(1-trityl-1H-tetrazol-5-yl)imidazo[1,2-a]pyridine

(This compound was used to the next reaction without furtherpurification.)

(4) 1-Bromo-2-(4-bromomethylphenyl)indolizine-3-carbonitrile

NMR (CDCl₃, δ): 4.56 (2H, s), 6.92 (1H, dt, J=1 Hz and 7 Hz); 7.17 (1H,ddd, J=1 Hz, 7 Hz and 8 Hz), 7.54 (2H, d, J=7 Hz), 7.60 (1H, m), 7.71(2H, d, J=7 Hz), 8.28 (1H, d, J=7 Hz)

(5) 3-Bromo-2-(4-bromomethylphenyl)indolizine-1-carbonitrile

NMR (CDCl₃, δ): 4.56 (2H, s), 6.95 (1H, dt, J=0.5 and 7 Hz), 7.19 (1H,ddd, J=0.5 Hz, 7 Hz and 8 Hz), 7.53 (2H, d, J=7 Hz), 7.65 (1H, m), 7.68(2H, d, J=7 Hz), 8.24 (1H, d, J=7 Hz)

(6)2-(4-Bromomethylphenyl)-4,5-dibromo-1-isopropylpyrrole-3-carbonitrile

(This compound was used to the next reaction without furtherpurification.)

Preparation 132

A mixture of 5-chloro-3-(4-methylphenyl)thiophene-2-carbonitrile (4.67g), trimethyltin azide (12.3 g) and xylene (100 ml) was heated underreflux for 15 hours. After standing for 3 days at ambient temperature,the precipitate was collected by vacuum filtration to give5-chloro-3-(4-methylphenyl)-2-(1H-tetrazol-5-yl)thiophene (14.7 g) as ayellowish powder. This powder was treated with trityl chloride (6.7 g)and 10N aqueous sodium hydroxide (2.4 ml) in dichloromethane (59 ml),and tetrahydrofuran (10 ml) at ambient temperature for 20 hours. Thereaction mixture was washed with brine and dried over magnesium sulfate.The solvents were evaporated in vacuo to give a residue which waspurified by silica gel column chromatography to afford5-chloro-3-(4-methylphenyl)-2-(1-trityl-1H-tetrazol-5-yl)thiophene (10.3g).

NMR (CDCl₃, δ): 2.35 (3H, s), 6.94-7.42 (20H)

Preparation 133

The following compound was obtained according to a similar manner tothat of the former half of Preparation 132.

2-(4-Methylphenyl)-3-(1H-tetrazol-5-yl)imidazo[1,2-a]pyridine.

NMR (CDCl₃ -CD₃ OD, δ): 1.97 (3H, s), 6.84 (2H, d, J=8 Hz), 6.93 (1H,dt, J=1 Hz and 7 Hz), 7.12 (2H, d, J=8 Hz), 7.35 (1H, dt, J=1 Hz and 8Hz), 8.56 (1H, ddd, J=1 Hz, 7 Hz and 8 Hz)

Preparation 134

The following compound was obtained according to a similar manner tothat of the latter half of Preparation 32.

2-(4-Methylphenyl)-3-(1-trityl-1H-tetrazol-5-yl)imidazo[1,2-a]pyridine

mp: 154°-156° C.

NMR (CDCl₃, δ): 2.93 (3H, s), 6.84 (1H, dd, J=1 Hz and 7 Hz), 6.96-7.11(8H, m), 7.14-7.40 (10H, m), 7.59-7.74 (3H, m), 8.95 (1H, br d, J=7 Hz)

Preparation 135

The following compounds were obtained according to a similar manner tothat of Preparation 9.

(1)2-Butyl-3-[4-(2-cyano-3-benzo[b]furyl)benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.92 (3H, t, J=7.5 Hz), 1.32-1.55 (2H, m), 1.74-1.95(2H, m), 2.88 (2H, t, J=7.5 Hz), 5.60 (2H, s), 7.21-7.80 (9H, m), 8.05(1H, dd, J=9.0 Hz, and 0.5 Hz), 8.37 (1H, dd, J=5.0 Hz and 0.5 Hz)

(2)2-Butyl-3-[4-(3-cyano-2-benzo[b]thienyl)benzyl]-3H-imidazo[4,5-b]pyridine

mp: 134°-135° C.

NMR (CDCl₃, δ): 0.94 (3H, t, J=7 Hz), 1.44 (2H, m), 1.86 (2H, m), 2.88(2H, t, J=7 Hz), 5.60 (2H, s), 7.22-7.60 (6H), 7.86 (2H, d, J=8 Hz),7.98 (1H, d, J=8 Hz), 8.07 (1H, d, J=8 Hz), 8.38 (1H, d, J=5 Hz)

(3)2-Butyl-3-[4-(1-bromo-3-cyano-2-indolizinyl)benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.92 (3H, t, J=7 Hz), 1.44 (2H, m), 1.86 (2H, m), 2.94(2H, t, J=7 Hz), 5.61 (2H, s), 6.90 (1H, dt, J=1 Hz and 7 Hz), 7.15 (1H,ddd, J=1 Hz, 7 Hz and 8 Hz), 7.28 (2H, d, J=7 Hz), 7.29 (1H, m), 7.57(1H, d, J=8 Hz), 7.67 (2H, d, J=8 Hz), 8.13 (1H, d, J=8 Hz), 8.25 (1H,d, J=7 Hz), 8.43 (1H, dd, J=1 Hz and 6 Hz)

(4)2-Butyl-3-[4-(3-bromo-1-cyano-2-indolizinyl)benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.91 (3H, t, J=7 Hz), 1.43 (2H, m), 1.86 (2H, m), 2.88(2H, t, J=7 Hz), 5.63 (2H, s), 6.98 (1H, dd, J=1 Hz and 7 Hz), 7.21 (1H,dd, J=1 Hz and 8 Hz), 7.28 (1H, m), 7.31 (2H, d, J=7 Hz), 7.68 (2H, d,J=7 Hz), 7.70 (1H, m), 8.11 (1H, dd, J=7 Hz and 1 Hz), 8.24 (1H, d, J=7Hz), 8.53 (1H, dd, J=5 Hz and 1 Hz)

(5)3-[4-(4-Cyano-1,2-dimethyl-3-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 122°-124° C.

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.5 Hz), 1.70-1.93 (2H, m), 2.20 (3H, s),2.71 (3H, s), 2.86 (2H, t, J=7.5 Hz), 3.58 (3H, s), 5.53 (2H, s), 7.05(1H, d, J=5 Hz), 7.10 (1H, s), 7.18 (2H, d, J=9 Hz), 7.32 (2H, d, J=9Hz), 8.23 (1H, d, J=5 Hz)

(6)3-[4-(3-Cyano-4,5-dibromo-1-isopropyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.02 (3H, t, J=8 Hz), 1.48 (6H, d, J=7 Hz), 1.83 (2H,m), 2.72 (3H, s), 2.87 (2H, t, J=8 Hz), 4.49 (1H, m), 5.56 (2H, s), 7.07(1H, d, J=5 Hz), 7.24 (2H, d, J=9 Hz), 7.39 (2H, d, J=9 Hz), 8.23 (1H,d, J=5 Hz)

(7)3-[4-(2-Chloro-4-cyano-1-methyl-3-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 150°-152° C.

NMR (CDCl₃, δ): 0.99 (3H, t, J=7.5 Hz), 1.66-1.90 (2H, m), 2.61 (3H, s),2.65 (3H, s), 2.80 (2H, m), 3.67 (3H, s), 5.50 (2H, s), 6.92 (1H, s),7.11-7.23 (3H, m), 7.50 (2H, d, J=9 Hz)

Preparation 136

The following compound was obtained according to similar manners tothose of Preparation 130 and 9, successively.

A mixture of3-[4-(5-bromo-3-cyano-1-propyl-2-pyrrolyl)benzyl]-7-methyl-3-propyl-3H-imidazo[4,5-b]pyridineand3-[4-(4-bromo-3-cyano-1-propyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine.

NMR (CDCl₃, δ): 0.67 (1.5H, t, J=8 Hz), 0.70 (1.5H, t, J=8 Hz), 0.99(3H, t, J=8 Hz), 1.57 (2H, m), 1.83 (2H, m), 2.74 (3H, br s), 2.91 (2H,m), 3.86 (2H, m), 5.57 (2H, s), 6.50 (0.5H, s), 7.10 (1H, d, J=5 Hz),7.19-7.41 (4.5H, m), 8.26 (0.5H, d, J=5 Hz), 8.27 (0.5H, d, J=5 Hz)

Preparation 137

The following compounds were obtained according to a similar manner tothat of Preparation 28.

(1)3-[4-(2-Chloro-4-cyano-1-methyl-3-pyrrolyl)benzyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine

mp: 155°-157° C.

NMR (CDCl₃, δ): 1.35 (3H, t, J=7.5 Hz), 2.60 (3H, s), 2.67 (3H, s), 2.86(2H, q), 3.67 (3H, s), 5.50 (2H, s), 6.92 (1H, s), 7.13-7.24 (3H, m),7.50 (2H, d, J=9 Hz)

(2) A mixture of3-[4-(4-bromo-3-cyano-1-ethyl-2-pyrrolyl)benzyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridineand3-[4-(5-bromo-3-cyano-1-ethyl-2-pyrrolyl)benzyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine.

NMR (CDCl₃, δ): 1.12-1.32 (6H, m), 2.60 (3H, s), 2.65 (3H, s), 2.82 (2H,t, J=8 Hz), 3.82-4.05 (2H, m), 5.54 (2H, s), 6.50 (0.4H, s), 6.93 (0.6H,s), 7.18-7.42 (4H, m)

Preparation 138

The following compounds were obtained according to a similar manner tothat of Preparation 105.

(1)3-[4-(3-Cyano-1-propyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.75 (3H, t, J=8 Hz), 1.00 (3H, t, J=8 Hz), 1.61 (2H,m), 1.81 (2H, m), 2.72 (3H, s), 2.88 (2H, t, J=8 Hz), 3.78 (2H, t, J=8Hz), 5.55 (2H, s), 6.47 (1H, d, J=3 Hz), 6.69 (1H, d, J=3 Hz), 7.06 (1H,d, J=5 Hz), 7.23 (2H, d, J=9 Hz), 7.33 (2H, d, J=9 Hz), 8.24 (1H, d, J=5Hz)

(2)3-[4-(3-Cyano-1-ethyl-2-pyrrolyl)benzyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine

mp: 171°-172° C.

NMR (CDCl₃, δ): 1.26 (3H, t, J=8 Hz), 1.36 (3H, t, J=8 Hz), 2.61 (3H,s), 2.66 (3H, s), 2.86 (2H, q, J=8 Hz), 3.87 (2H, q, J=8 Hz), 5.53 (2H,s), 6.49 (1H, d, J=3 Hz), 6.70 (1H, d, J=3 Hz), 6.95 (1H, s), 7.23 (2H,d, J=9 Hz), 7.35 (2H, d, J=9 Hz)

(3)3-[4-(3-Cyano-1-isopropyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.01 (3H, t, J=8 Hz), 1.33 (6H, d, J=7 Hz), 1.81 (2H,m), 2.70 (3H, s), 2.86 (2H, t, J=8 Hz), 4.31 (1H, m), 5.55 (2H, s), 6.50(1H, d, J=3 Hz), 6.79 (1H, d, J=3 Hz), 7.05 (1H, d, J=5 Hz), 7.23 (2H,d, J=9 Hz), 7.32 (2H, d, J=9 Hz), 8.23 (1H, d, J=5 Hz)

Preparation 139

The following compound was obtained according to similar manners tothose of Preparation 27 and 28, successively.

A mixture of3-[4-(4-bromo-3-cyano-1-ethyl-2-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridineand3-[4-(5-bromo-3-cyano-1-ethyl-2-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.96 (3H, t, J=8 Hz), 1.21 (3H, t, J=8 Hz), 1.76 (2H,m), 2.59 (3H, s), 2.63 (3H, s), 2.76 (2H, t, J=8 Hz), 3.85-4.05 (2H, m),5.51 (2H, s), 6.91 (0.9H, s), 7.16-7.57 (4.1H, m)

Preparation 140

The following compound was obtained according to a similar manner tothat of Preparation 105.

3-[4-(3-Cyano-1-ethyl-2-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.97 (3H, t, J=8 Hz), 1.26 (3H, t, J=8 Hz), 1.76 (2H,m), 2.60 (3H, s), 2.64 (3H, s), 2.76 (2H, dd, J=7 Hz and 8 Hz), 3.88(2H, q, J=8 Hz), 5.52 (2H, s), 6.49 (1H, d, J=3 Hz), 6.70 (1H, d, J=3Hz), 6.90 (1H, s), 7.23 (2H, d, J=9 Hz), 7.84 (2H, d, J=9 Hz)

Preparation 141

A mixture of (4-methoxycarbonylbenzoyl)acetonitrile (80.0 g),2-aminopropanone diethyl acetal (58.0 g) and toluene (370 ml) wasrefluxed for 15 hours under nitrogen atmosphere. The mixture wasevaporated in vacuo. The residue was purified by silica gel columnchromatography to afford a mixture of(E)-3-(2,2-diethoxy-1-methylethylamino)-3-(4-methoxycarbonylphenyl)acrylonitrileand(Z)-3-(2,2-diethoxy-1-methylethylamino)-3-4-methoxycarbonylphenyl)acrylonitrileas a brown oil (117.6 g).

NMR (CDCl₃, δ): 1.23 (6H, t, J=7.0 Hz), 1.27 (3H, d, 3.95 (3H, s), 4.03(2/5H, s), 4.17 (3/5H, s), 4.36 (2/5H, d, J=3.5 Hz), 4.46 (3/5H, d,J=3.5 Hz), 4.69 (3/5H, d, J=8.0 Hz), 5.07 (2/5H, d, J=10.0 Hz), 7.50(4/5H, d, J=8.0 Hz), 7.61 (6/5H, d, J=8.0 Hz), 8.08 (4/5H, d, J=8.0 Hz),8.11 (6/5H, d, J=8.0 Hz)

Preparation 142

A mixture (117.0 g) of(E)-3-(2,2-diethoxy-1-methylethylamino-3-(4-methoxycarbonylphenyl)acrylonitrileand(Z)-3-(2,2-diethoxy-1-methylethylamino)-3-(4-methoxycarbonylphenyl)acrylonitrilewas treated with trifluoroacetic acid (200 ml) at 0° C. for 30 minutesand then at ambient temperature for 30 minutes. To the mixture ethylacetate (300 ml) was added at 0° C. and this mixture was stirred at 0°C. for 15 minutes. The precipitates were collected by vacuum filtrationto afford 2-(4-methoxycarbonylphenyl)-5-methylpyrrole-3-carbonitrile asan orange powder (54.8 g).

mp: 201°-205° C.

NMR (CDCl₃, δ): 2.35 (3H, s), 3.96 (3H, s), 6.28 (1H, d, J=2.5 Hz), 7.74(2H, d, J=9.0 Hz), 8.10 (2H, d, J=9.0 Hz), 8.60 (1H, br s)

Preparation 143

The following compounds were obtained according to a similar manner tothat of Preparation 96.

(1) 2-(4-Methoxycarbonylphenyl)-1,5-dimethylpyrrole-3-carbonitrile

mp: 138°-139.5° C.

NMR (CDCl₃, δ): 2.29 (3H, s), 3.51 (3H, s), 3.96 (3H, s), 6.27 (1H, s),7.52 (2H, d, J=9.0 Hz), 8.16 (2H, d, J=9.0 Hz)

(2) 1-Ethyl-2-(4-methoxycarbonylphenyl)-5-methylpyrrole-3-carbonitrilemp: 84°-85.5° C.

NMR (CDCl₃, δ): 1.21 (3H, t, J=7.0 Hz), 2.31 (3H, s), 3.91 (2H, q, J=7.0Hz), 3.97 (3H, s), 6.26 (1H, s), 7.51 (2H, d, J=9.0 Hz), 8.16 (2H, d,J=9.0 Hz)

(3) 5-Chloro-1-methyl-2-(4-methylphenyl)pyrrole-3-carbonitrile

NMR (CDCl₃, δ): 2.42 (3H, s), 3.54 (3H, s), 6.41 (1H, s), 7.32 (4H, s)

(4) 5-Chloro-1-ethyl-2-(4-methylphenyl)pyrrole-3-carbonitrile

NMR (CDCl₃, δ): 1.25 (3H, t, J=7 Hz), 2.41 (3H, s), 3.92 (2H, q, J=7Hz), 6.49 (1H, s), 7.30 (4H, s)

Preparation 144

The following compound was obtained according to a similar manner tothat of Preparation 1.

5-Chloro-2-(4-methylphenyl)pyrrole-3-carbonitrile

NMR (CDCl₃, δ): 2.39 (3H, s), 6.37 (1H, d, J=3 Hz), 7.27 (2H, d, J=9Hz), 7.54 (2H, d, J=9 Hz), 8.64 (1H, br s)

Preparation 145

The following compounds were obtained according to a similar manner tothat of Preparation 37.

(1) 2-(4-Hydroxymethylphenyl)-1,5-dimethylpyrrole-3-carbonitrile

mp: 108°-111° C.

NMR (CDCl₃, δ): 1.96 (1H, bt, J=4.0 Hz), 2.28 (3H, s), 3.49 (3H, s),4.75 (2H, d, J=4.0 Hz), 6.22 (1H, s), 7.41 (2H, d, J=9.0 Hz), 7.49 (2H,d, J=9.0 Hz)

(2) 1-Ethyl-2-(4-hydroxymethylphenyl)-5-methylpyrrole-3-carbonitrile

mp: 91°-94.5° C.

NMR (CDCl₃, δ): 1.18 (3H, t, J=7.0 Hz), 2.19 (1H, br s), 2.29 (3H, s),3.87 (2H, q, J=7.0 Hz), 4.73 (2H, s), 6.20 (1H, s), 7.40 (2H, d, J=9.0Hz), 7.48 (2H, d, J=9.0 Hz)

Preparation 146

The following compounds were obtained according to a similar manner tothat of Preparation 60.

(1)2-(4-Methanesulfonyloxymethylphenyl)-1,5-dimethylpyrrole-3-carbonitrile

mp: 89°-94° C.

NMR (CDCl₃, δ): 2.28 (3H, s), 3.01 (3H, s), 3.49 (3H, s), 5.29 (2H, s),6.25 (1H, s), 7.47 (2H, d, J=9.0 Hz), 7.56 (2H, d, J=9.0 Hz)

(2)1-Ethyl-2-(4-methanesulfonyloxymethylphenyl)-5-methylpyrrole-3-carbonitrile

mp: 104.5°-108° C.

NMR (CDCl₃, δ): 1.20 (3H, t, J=7.0 Hz), 2.31 (3H, s), 3.01 (3H, s), 3.89(2H, q, J=7.0 Hz), 5.29 (2H, s), 6.24 (1H, s), 7.47 (2H, d, J=9.0 Hz),7.56 (2H, d, J=9.0 Hz)

Preparation 147

The following compounds were obtained according to a similar manner tothat of Preparation 7.

(1) 2-(4-Bromomethylphenyl)-5-chloro-1-methylpyrrole-3-carbonitrile

NMR (CDCl₃, δ): 4.54 (2H, s), 6.45 (1H, s), 7.41 (2H, d, J=9 Hz), 7.53(2H, d, J=9 Hz)

(2) 2-(4-Bromomethylphenyl)-5-chloro-1-ethylpyrrole-3-carbonitrile

NMR (CDCl₃, δ): 1.28 (3H, t, J=7 Hz), 3.97 (2H, q, J=7 Hz), 4.52 (2H,s), 6.42 (1H, s), 7.40 (2H, d, J=9 Hz), 7.52 (2H, d, J=9 Hz)

Preparation 148

The following compounds were obtained according to a similar manner tothat of Preparation 9.

(1)3-[4-(3-Cyano-5-chloro-1-ethyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.00 (3H, t, J=7 Hz), 1.20 (3H, t, J=7 Hz), 1.81 (2H,m), 2.71 (3H, s), 2.82 (2H, t, J=7 Hz), 3.91 (2H, q, J=7 Hz), 5.54 (2H,s), 6.40 (1H, s), 7.04 (1H, d, J=5 Hz), 7.19 (2H, d, J=9 Hz), 7.33 (2H,d, J=9 Hz), 8.23 (1H, d, J=5 Hz)

(2)3-[4-(3-Cyano-5-chloro-1-methyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 132°-134° C.

NMR (CDCl₃, δ): 1.01 (3H, t, J=7 Hz), 1.82 (2H, m), 2.70 (3H, s), 2.83(2H, t, J=7 Hz), 3.50 (3H, s), 5.55 (2H, s), 6.41 (1H, s), 7.05 (1H, d,J=5 Hz), 7.24 (2H, d, J=9 Hz), 7.36 (2H, d, J=9 Hz), 8.21 (1H, d, J=5Hz)

(3)3-[4-(5-Chloro-3-cyano-1-ethyl-2-pyrrolyl)benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.19 (3H, t, J=8 Hz), 1.32 (3H, t, J=8 Hz), 2.60 (3H,s), 2.65 (3H, s), 2.81 (2H, q, J=8 Hz), 3.90 (2H, q, J=8 Hz), 5.50 (2H,s), 6.40 (1H, s), 6.90 (1H, s), 7.19 (2H, d, J=9 Hz), 7.34 (2H, d, J=9Hz)

(4)3-[4-(5-Chloro-3-cyano-1-methyl-2-pyrrolyl)benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.36 (3H, t, J=7 Hz), 2.60 (3H, s), 2.64 (3H, s), 2.82(2H, q, J=7 Hz), 3.50 (3H, s), 5.51 (2H, s), 6.41 (1H, s), 6.92 (1H, s),7.24 (2H, d, J=9 Hz), 7.36 (2H, d, J=9 Hz)

(5)3-[4-(5-Chloro-3-cyano-1-ethyl-2-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 131°-135° C.

NMR (CDCl₃, δ): 0.96 (3H, t, J=7 Hz), 1.21 (3H, t, J=7 Hz), 1.76 (2H,m), 2.60 (3H, s), 2.64 (3H, s), 2.77 (2H, t, J=7 Hz), 3.91 (2H, q, J=7Hz), 5.52 (2H, s), 6.40 (1H, s), 6.92 (1H, s), 7.25 (2H, d, J=9 Hz),7.34 (2H, d, J=9 Hz)

(6)3-[4-(5-Chloro-3-cyano-1-methyl-2-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.98 (3H, t, J=7 Hz), 1.78 (2H, m), 2.60 (3H, s), 2.63(3H, s), 2.76 (2H, t, J=7 Hz), 3.50 (3H, s), 5.51 (2H, s), 6.40 (1H, s),6.91 (1H, s), 7.22 (2H, d, J=9 Hz), 7.34 (2H, d, J=9 Hz)

(7)3-[4-(3-Cyano-1,5-dimethyl-2-pyrrolyl)benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 156°-157° C.

NMR (CDCl₃, δ): 1.34 (3H, t, J=7.5 Hz), 2.25 (3H, s), 2.60 (3H, s), 2.65(3H, s), 2.82 (2H, q, J=7.5 Hz), 3.42 (3H, s), 5.51 (2H, s), 6.21 (1H,s), 6.91 (1H, s), 7.22 (2H, d, J=9.0 Hz), 7.35 (2H, d, J=9.0 Hz)

(8)3-[4-(3-Cyano-1-ethyl-5-methyl-2-pyrrolyl)benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 159°-162° C.

NMR (CDCl₃, δ): 1.15 (3H, t, J=7.0 Hz), 1.32 (3H, t, J=7.5 Hz), 2.28(3H, s), 2.61 (3H, s), 2.66 (3H, s), 2.84 (2H, q, J=7.5 Hz), 3.81 (2H,q, J=7.0 Hz), 5.51 (2H, s), 6.20 (1H, s), 6.91 (1H, s), 7.21 (2H, d,J=9.0 Hz), 7.35 (2H, d, J=9.0 Hz)

(9)3-[4-(3-Cyano-1,5-dimethyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 111°-113° C.

NMR (CDCl₃, δ): 1.01 (3H, t, J=7.5 Hz), 1.71-1.92 (2H, m), 2.24 (3H, s),2.70 (3H, s), 2.84 (2H, t, J=7.5 Hz), 3.42 (3H, s), 5.54 (2H, s), 6.21(1H, s), 7.03 (1H, d, J=5.0 Hz), 7.22 (2H, d, J=9.0 Hz), 7.37 (2H, d,J=9.0 Hz), 8.21 (1H, d, J=5.0 Hz)

(10)3-[4-(3-Cyano-1-ethyl-5-methyl-2-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 113°-115° C.

NMR (CDCl₃, δ): 1.00 (3H, t, J=7.5 Hz), 1.15 (3H, t, J=7.0 Hz),1.70-1.91 (2H, m), 2.28 (3H, s), 2.70 (3H, s), 2.83 (2H, t, J=7.5 Hz),3.82 (2H, q, J=7.0 Hz), 5.54 (2H, s), 6.20 (1H, s), 7.05 (1H, d, J=5.0Hz), 7.21 (2H, d, J=9.0 Hz), 7.35 (2H, d, J=9.0 Hz), 8.21 (1H, d, J=5.0Hz)

(11)3-[4-(3-Cyano-1,5-dimethyl-2-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 118°-120° C.

NMR (CDCl₃, δ): 0.98 (3H, t, J=7.5 Hz), 1.67-1.89 (2H, m), 2.25 (3H, s),2.60 (3H, s), 2.63 (3H, s), 2.78 (2H, t, J=7.5 Hz), 3.42 (3H, s), 5.51(2H, s), 6.21 (1H, s), 6.91 (1H, s), 7.21 (2H, d, J=9 Hz), 7.35 (2H, d,J=7.5 Hz)

(12)3-[4-(3-Cyano-1-ethyl-5-methyl-2-pyrrolyl)benzyl]5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 169°-170° C.

NMR (CDCl₃, δ): 0.98 (3H, t, J=7 Hz), 1.14 (3H, t, J=7 Hz), 1.77 (2H,m), 2.27 (3H, s), 2.61 (3H, s), 2.65 (3H, s), 2.78 (2H, t, J=7 Hz), 3.81(2H, q, J=7 Hz), 5.52 (2H, s), 6.20 (1H, s), 6.91 (1H, s), 7.21 (2H, d,J=9 Hz), 7.35 (2H, d, J=9 Hz)

(13)3-[4-(2-Bromo-4-cyano-1-methyl-3-pyrrolyl)benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 151°-152° C.

NMR (CDCl₃, δ): 1.33 (3H, t, J=7.5 Hz), 2.60 (3H, s), 2.64 (3H, s), 2.82(2H, q, J=7.5 Hz), 3.69 (3H, s), 5.50 (2H, s), 6.90 (1H, s), 7.19 (2H,d, J=9 Hz), 7.30 (1H, s), 7.48 (2H, d, J=9 Hz)

(14)3-[4-(2-Bromo-4-cyano-1-methyl-3-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 142°-143° C.

NMR (CDCl₃, δ): 0.98 (3H, t, J=7.5 Hz), 1.65-1.87 (2H, m), 2.60 (3H, s),2.64 (3H, s), 2.78 (2H, t, J=7.5 Hz), 3.69 (3H, s), 5.50 (2H, s), 6.90(1H, s), 7.17 (2H, d, J=9 Hz), 7.30 (1H, s), 7.48 (2H, d, J=9 Hz)

EXAMPLE 1

A mixture of2-butyl-3-[4-(3,4-dichloro-2-cyano-1-pyrrolyl)benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine(490 mg) and trimethyltin azide (690 mg) in xylene (5 ml) was stirred at120° C. for 22 hours. After cooled to ambient temperature, the mixturewas treated with aqueous 1N sodium hydroxide (10 ml) for 4 hours. Thesuspension was filtered. The filtrate was washed with diisopropyl ether,adjusted to pH 4 with aqueous 1N-hydrochloric acid, and concentrated invacuo. The residue was purified by column chromatography on silica gel(elution by methanol/dichloromethane=1/8) to give2-butyl-3-[4-[3,4-dichloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine(516 mg) as an amorphous solid.

NMR (DMSO-d₃, δ): 0.83 (3H, t, J=7.5 Hz), 1.22-1.44 (2H, m), 1.57-1.74(2H, m), 2.58 (3H, s), 2.85 (2H, t, J=7.5 Hz), 5.58 (2H, s), 6.81 (1H,s), 7.10 (1H, d, J=4.5 Hz), 7.20 (2H, d, J=8.5 Hz), 7.28 (2H, d, J=8.5Hz), 8.18 (1H, d, J=4.5 Hz)

Example 2

The following compounds were obtained according to a similar manner tothat of Example 1.

(1)3-[4-[4-Bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 188°-191° C.

NMR (DMSO-d₆, δ): 0.88 (3H, t, J=7.5 Hz), 1.37 (2H, m), 1.68 (2H, m),2.57 (3H, s), 5.55 (2H, s), 6.87 (1H, d, J=2.3 Hz), 7.09 (1H, d, J=5Hz), 7.19 (4H, m), 7.40 (1H, d, J=2.3 Hz), 8.17 (1H, d, J=5 Hz)

(2)2-Butyl-3-[4-[2-chloro-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 147° C.

NMR (DMSO-d₆, δ): 0.82 (3H, t, J=7.5 Hz), 1.22-1.45 (2H, m), 1.58-1.77(2H, m), 2.86 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.41 (1H, d, J=4.5 Hz),6.74 (1H, d, J=4.5 Hz), 7.21 (4H, s), 7.28 (1H, dd, J=8.0 Hz and 5.0Hz), 8.03 (1H, dd, J=8.0 Hz and 1.0 Hz), 8.33 (1H, dd, J=5.0 Hz and 1.0Hz)

(3) 2-Butyl-3-[4-[4-nitro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.88 (3H, t, J=7.5 Hz), 1.27-1.49 (2H, m), 1.64-1.83(2H, m), 2.89 (2H, t, J=7.5 Hz), 5.56 (2H, s),7.03 (1H, d, J=1.5 Hz),7.19 (2H, d, J=8.0 Hz), 7.27 (1H, dd, J=7.5 Hz and 5.0 Hz), 7.29 (2H, d,J=8.0 Hz), 8.01 (1H, dd, J=7.5 Hz & 1.0 Hz), 8.19 (1H, d, J=1.5 Hz),8.31 (1H, dd, J=5.0 Hz and 1.0 Hz)

(4)2-Butyl-3-[4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 98°-101° C.

NMR (CD₃ OD, δ): 0.93 (3H, t, J=7.5 Hz), 1.44 (2H, m), 1.80 (2H, m),2.90 (2H, dd, J=7 Hz & 7 Hz), 5.57 (2H, s), 6.42 (1H, dd, J=3.5 Hz & 3Hz), 6.94 (1H, dd, J=3.5 Hz & 2 Hz), 7.04 (1H, dd, J=3 Hz & 2 Hz), 7.21(4H, s), 7.32 (1H, dd, J=8 Hz & 5 Hz), 8.04 (1H, dd, J=8 Hz & 1 Hz),8.35 (1H, dd, J=5 Hz & 1 Hz)

(5)2-Butyl-3-[4-[2-(1H-tetrazol-5-yl)-1-indolyl]benzyl]-3H-imidazo[4,5-b]pyridine(6)2-Butyl-3-[4-[2-chloro-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridineEXAMPLE 3

To a solution of2-butyl-3-[4-[3,4-dichloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine(496 mg) in hot ethanol (7.5 ml) was added a solution of sodiumbicarbonate (86.6 mg) in water (4 ml) in one portion. The mixture wasstirred at 80° C. for 5 minutes and concentrated in vacuo. The residuewas dissolved in ethanol (6 ml). The ethanolic solution was filteredthrough a millipor filter. The filtrate was evaporated under reducedpressure. The residue was dissolved in water (5 ml) and lyophilized toyield sodium salt of2-butyl-3-[4-[3,4-dichloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine(466 mg) as a solid.

NMR (D₂ O, δ): 0.43 (3H, t, J=7.5 Hz), 0.80-1.01 (2H, m), 1.14-1.34 (2H,m), 2.31 (3H, s), 2.61 (2H, t, J=7.5 Hz), 5.31 (2H, s), 6.54 (1H, s),6.69 (2H, d, J=8.5 Hz), 6.79 (1H, d, J=5.0 Hz), 6.90 (2H, d, J=8.5 Hz),7.90 (1H, d, J=5.0 Hz)

EXAMPLE 4

The following compounds were obtained according to a similar manner tothat of Example 3.

(1) Sodium salt of3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 154°-168° C.

NMR (D₂ O, δ): 0.51 (3H, t, J=7.5 Hz), 0.87-1.08 (2H, m), 1.15-1.36 (2H,m), 2.30 (3H, s), 2.55 (2H, t, J=7.5 Hz), 5.18 (2H, s), 6.26 (1H, d,J=1.5 Hz), 6.48 (1H, d, J=1.5 Hz), 6.51 (2H, d, J=8.0 Hz), 6.69 (2H, d,J=8.0 Hz), 6.71 (1H, d, J=5.0 Hz), 7.78 (1H, d, J=5.0 Hz)

(2) Sodium salt of2-butyl-3-[4-[2-chloro-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.60 (3H, t, J=7 Hz), 1.08 (2H, m), 1.40 (2H, m), 2.70(2H, t, J=7 Hz), 5.42 (2H, s), 6.19 (1H, d, J=4 Hz), 6.63 (1H, d, J=4Hz), 6.90 (2H, d, J=9 Hz), 7.00 (2H, d, J=9 Hz), 7.20 (1H, dd, J=9 Hz &6 Hz), 7.90 (1H, dd, J=9 Hz & 1 Hz), 8.17 (1H, dd, J=6 Hz & 1 Hz)

(3) Sodium salt of2-butyl-3-[4-[4-nitro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 166°-179° C.

NMR (D₂ O, δ): 0.71 (3H, t, J=7.5 Hz), 1.05-1.27 (2H, m), 1.41-1.61 (2H,m), 2.70 (2H, t, J=7.5 Hz), 5.42 (2H, s), 6.83 (2H, d, J=9.0 Hz), 6.94(2H, d, J=9.0 Hz), 7.12 (1H, d, J=1.5 Hz), 7.21 (1H, dd, J=8 Hz & 5 Hz),7.64 (1H, d, J=1.5 Hz), 7.92 (1H, dd, J=8.0 Hz & 1.0 Hz), 8.12 (1H, dd,J=5.0 Hz & 1.0 Hz)

(4) Sodium salt of2-butyl-3-[4-[2-(1H-tetrazol-5-yl)-1-indolyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 187°-192° C. (dec.)

NMR (D₂ O+CD₃ OD, δ): 0.50 (3H, t, J=7.5 Hz), 0.92 (2H, m), 1.28 (2H,m), 2.50 (2H, t, J=7.5 Hz), 5.26 (2H, s), 6.50-6.82 (3H, m), 6.63 (2H,d, J=8 Hz), 6.80 (2H, d, J=8 Hz), 6.98 (1H, s), 7.12 (1H, dd, J=8 Hz & 5Hz), 7.37 (1H, d, J=8 Hz), 7.86 (1H, d, J=8 Hz), 8.08 (1H, d, J=5 Hz)

(5) Sodium salt of2-butyl-3-[4-[2-chloro-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 154°-157° C.

NMR (D₂ O, δ): 0.72 (3H, t, J=7.5 Hz), 1.21 (2H, m), 1.49 (2H, m), 2.60(3H, s), 2.87 (2H, t, J=6 Hz), 5.54 (2H, s), 6.25 (1H, d, J=4 Hz), 6.84(1H, d, J=4 Hz), 6.90 (2H, d, J=9 Hz), 7.05 (1H, d, J=5 Hz), 7.14 (2H,d, J=9 Hz), 8.15 (1H, d, J=5 Hz)

EXAMPLE 5

The following compounds were obtained according to a similar manner tothat of Example 1.

(1)3-[4-[2-Bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.90 (3H, t, J=7.5 Hz), 1.40 (2H, m), 1.70 (2H, m), 3.41(2H, m), 5.62 (2H, s), 6.47 (1H, d, J=4 Hz), 6.90 (1H, d, J=4 Hz), 7.15(1H, d, J=5 Hz), 7.23 (4H, s), 8.20 (1H, d, J=5 Hz)

(2)3-[4-[4-Bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]-2-fluorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.89 (3H, t, J=7.5 Hz), 1.27-1.49 (2H, m), 1.62-1.82(2H, m), 2.57 (3H, s), 2.86 (2H, t, J=7.5 Hz), 5.57 (2H, s), 6.85 (1H,d, J=1.0 Hz), 6.92 (1H, d, J=9 Hz), 7.03 (1H, dd, J=9.0 Hz & 1.5 Hz),7.09 (1H, d, J=5.0 Hz), 7.33 (1H, dd, J=11.0 Hz & 1.5 Hz), 7.45 (1H, d,J=1.0 Hz), 8.14 (1H, d, J=5.0 Hz)

(3)3-[4-[4-Bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]-benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 179°-186° C.

NMR (DMSO-d₆, δ): 0.94 (3H, t, J=7.5 Hz), 1.62-1.86 (2H, m), 2.58 (3H,s), 2.82 (2H, t, J=7.5 Hz), 5.53 (2H, s), 6.81 (1H, d, J=1.0 Hz), 7.09(1H, d, J=5 Hz), 7.16 (2H, d, J=9.0 Hz), 7.22 (2H, d, J=9.0 Hz), 7.39(1H, d, J=1.0 Hz), 8.16 (1H, d, J=5.0 Hz)

(4)2-Butyl-7-methyl-3-[2-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]-5-pyridylmethyl]-3H-imidazo[4,5-b]pyridine

mp: 148°-154° C.

NMR (DMSO-d₆, δ): 0.89 (3H, t, J=7.5 Hz), 1.28-1.49 (2H, m), 1.61-1.81(2H, m), 2.56 (3H, s), 2.90 (2H, t, J=7.5 Hz), 5.57 (2H, s), 6.46 (1H,t, J=4.0 Hz), 6.86 (1H, dd, J=4.0 Hz & 1.0 Hz), 7.11 (1H, d, J=5.0 Hz),7.38 (1H, d, J=8.5 Hz), 7.50 (1H, dd, J=4.0 Hz & 1.0 Hz), 7.69 (1H, dd,J=8.5 Hz & 1.5 Hz), 8.17 (1H, d, J=5.0 Hz), 8.31 (1H, d, J=1 5 Hz)

(5)3-[2-[2-Bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]-5-pyridylmethyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 98°-114° C.

NMR (DMSO-d₆, δ): 0.87 (3H, t, J=7.5 Hz), 1.25-1.48 (2H, m), 1.59-1.78(2H, m), 2.57 (3H, s), 2.90 (2H, t, J=7.5 Hz), 5.69 (2H, s), 6.58 (1H,d, J=4.5 Hz), 6.96 (1H, d, J=4.5 Hz), 7.11 (1H, d, J=5.0 Hz), 7.48 (1H,d, J=7.5 Hz), 7.73 (1H, dd, J=7.5 Hz & 1.5 Hz), 8.20 (1H, d, J=5.0 Hz),8.48 (1H, d, J=1.5 Hz)

(6)3-[3-Bromo-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.89 (3H, t, J=7.5 Hz), 1.29-1.50 (2H, m), 1.62-1.80(2H, m), 2.58 (3H, s), 2.89 (2H, t, J=7.5 Hz), 5.61 (2H, s), 6.43 (1H,t, J=4.0 Hz), 6.97 (1H, dd, J=4.0 Hz & 1.0 Hz), 7.05-7.15 (1H, m),7.11(1H, d, J=5.0 Hz), 7.16 (1H, dd, J=8.5 Hz & 1.0 Hz), 7.43 (1H, d,J=8.5 Hz), 7.64 (1H, d, J=1.0 Hz), 8.20 (1H, d, J=5.0 Hz)

(7)3-[3-Bromo-4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.89 (3H, t, J=7.5 Hz), 1.28-1.50 (2H, m), 1.62-1.80(2H, m), 2.58 (3H, s), 2.88 (2H, t, J=7.5 Hz), 5.61 (2H, s), 6.93 (1H,d, J=1.5 Hz), 7.11 (1H, d, J=5.0 Hz), 7.15 (1H, dd, J=8.5 Hz & 1.0 Hz),7.31 (1H, d, J=1.5 Hz), 7.45 (1H, d, J=8.5 Hz), 7.63 (1H, d, J=1.0 Hz),8.19 (1H, d, J=5.0 Hz)

(8)3-[4-[2-Bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]-3-chlorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ -CD₃ OD, δ): 0.93 (3H, t, J=7.5 Hz), 1.44 (2H, m), 1.74 (2H,m), 2.73 (3H, s), 3.05 (2H, dd, J=8 Hz & 7 Hz), 5.72 (2H, s), 6.53 (1H,d, J=4 Hz), 6.98 (1H, d, J=4 Hz), 7.32-7.34 (2H, m), 7.37-7.45 (2H, m),8.37 (1H, d, J=5 Hz)

(9)3-[4-[4-Bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]-3-chlorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ +CD₃ OD, δ): 0.95 (3H, t, J=7.5 Hz), 1.45 (2H, m), 1.77 (2H,m), 2.70 (3H, s), 2.94 (2H, t, J=7.5 Hz), 5.59 (2H, s), 6.93 (1H, d,J=1.9 Hz), 6.95 (1H, d, J=1.9 Hz), 7.13 (1H, d, J=5 Hz), 7.15 (1H, d,J=8.1 Hz, 1.9 Hz), 7.29 (1H, d, J=1.9 Hz), 7.38 (1H, d, J=8.1 Hz), 8.20(1H, d, J=5 Hz)

(10)3-[4-[4-Bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]-2-chlorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ -CD₃ OD, δ): 0.94 (3H, t, J=7.5 Hz), 1.44 (2H, m), 1.75 (2H,m), 2.70 (3H, s), 2.88 (2H, t, J=8 Hz), 5.65 (2H, s), 6.58 (1H, d, J=8Hz), 6.92 (1H, d, J=2 Hz), 7.02 (1H, dd, J=8 Hz & 2 Hz), 7.09 (1H, d,J=2 Hz), 7.14 (1H, d, J=5 Hz), 7.47 (1H, d, J=2 Hz), 8.18 (1H, d, J=5Hz)

(11) 3-[4-[2-Bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ -CD₃ OD, 6): 0.96 (3H, t, J=7.5 Hz), 1.74 (2H, m), 2.69 (3H,s), 2.86 (2H, t, J=8 Hz), 5.60 (2H, s), 6.45 (1H, d, J=4 Hz), 6.86 (1H,d, J=4 Hz), 7.13 (1H, d, J=5 Hz), 7.22 (4H, s), 8.20 (1H, d, J=5 Hz)

(12)2-Butyl-7-methyl-3-[3-nitro-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.88 (3H, t, J=7 Hz), 1.39 (2H, m), 1.73 (2H, m), 2.92(2H, t, J=7 Hz), 5.72 (2H, s), 6.45 (1H, t, J=3 Hz), 6.96 (1H, dd, J=3Hz & 1 Hz), 7.12 (1H, d, J=4 Hz), 7.19 (1H, d, J=1 Hz), 7.48 (1H, dd,J=7 Hz & 1 Hz), 7.57 (1H, d, J=7 Hz), 8.10 (1H, d, J=1 Hz), 8.19 (1H, d,J=4 Hz)

(13)2-Butyl-3-[3-chloro-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ -CD₃ OD, δ): 0.90 (3H, t, J=7.5 Hz), 1.40 (2H, m), 1.70 (2H,m), 2.64 (3H, s), 2.87 (2H, t, J=8 Hz), 5.54 (2H, s), 6.40 (1H, dd, J=4Hz & 3 Hz), 6.85 (1H, dd, J=3 Hz & 1 Hz), 6.90 (1H, dd, J=4 Hz & 1 Hz),7.09 (1H, d, J=5 Hz), 7.10 (1H, dd, J=8 Hz & 2 Hz), 7.23 (1H, d, J=2Hz), 7.32 (1H, d, J=8 Hz), 8.14 (1H, d, J=5 Hz)

EXAMPLE 6

The following compounds were obtained according to a similar manner tothat of Example 3.

(1) Sodium salt of3-[4-[2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.58 (3H, t, J=7.5 Hz), 1.06 (2H, m), 1.31 (2H, m), 2.44(3H, s), 2.71 (2H, t, J=6 Hz), 5.38 (2H, s), 6.26 (1H, d, J=4 Hz), 6.66(1H, d, J=4 Hz), 7.35 (2H, d, J=8 Hz), 7.43 (1H, d, J=5 Hz), 7.46 (2H,d, J=8 Hz), 7.97 (1H, d, J=5 Hz)

(2) Sodium salt of3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]-2-fluorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 153°-179° C.

NMR (D₂ O, δ): 0.58 (3H, t, J=7.5 Hz), 0.95-1.17 (2H, m), 1.25-1.46 (2H,m), 2.35 (3H, s), 2.63 (2H, t, J=7.5 Hz), 5.27 (2H, s), 6.29-6.43 (1H,m), 6.37 (1H, d, J=1.0 Hz), 6.49-6.63 (2H, m), 6.53 (1H, d, J=1.0 Hz),6.73 (1H, d, J=5.0 Hz), 7.83 (1H, d, J=5.0 Hz)

(3) Sodium salt of3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 157°-178° C.

NMR (D₂ O, δ): 0.78 (3H, t, J=7.5 Hz), 1.40-1.62 (2H, m), 2.47 (3H, s),2.70 (2H, t, J=7.5 Hz), 5.35 (2H, s), 6.52 (1H, d, J=1.0 Hz), 6.64 (2H,d, J=9.0 Hz), 6.65 (1H, d, J=1.0 Hz), 6.82 (2H, d, J=9.0 Hz), 6.93 (1H,d, J=5.0 Hz), 7.93 (1H, d, J=5.0 Hz)

(4) Sodium salt of2-butyl-7-methyl-3-[2-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]-5-pyridylmethyl]-3H-imidazo[4,5-b]pyridine

mp: 123°-148° C.

NMR (D₂ O, δ): 0.74 (3H, t, J=7.5 Hz), 1.12-1.33 (2H, m), 1.39-1.59 (2H,m), 2.50 (3H, s), 2.82 (2H, t, J=7.5 Hz), 5.42 (2H, s), 6.40 (1H, t,J=3.5 Hz), 6.65 (1H, d, J=8.0 Hz), 6.73 (1H, dd, J=3.5 Hz & 1.0 Hz),6.98 (1H, d, J=5.0 Hz), 7.10 (1H, dd, J=3.5 Hz, 1.0 Hz), 7.28 (1H, dd,J=8.0 Hz & 1.5 Hz), 7.97 (1H, d, J=5.0 Hz), 8.17 (1H, d, J=1.5 Hz)

(5) Sodium salt of3-[2-[2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]-5-pyridylmethyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 132°-157° C.

NMR (D₂ O, δ): 0.68 (3H, t, J=7.5 Hz), 1.06-1.28 (2H, m), 1.33-1.52 (2H,m), 2.50 (3H, s), 2.84 (2H, t, J=7.5 Hz), 5.56 (2H, s), 6.41 (1H, d,J=4.5 Hz), 6.73 (1H, d, J=4.5 Hz), 7.03 (1H, d, J=5.0 Hz), 7.09 (1H, d,J=9 Hz), 7.52 (1H, dd, J=9.0 Hz & 1.5 Hz), 8.04 (1H, d, J=5.0 Hz), 8.31(1H, d, J=1.5 Hz)

(6) Sodium salt of3-[3-bromo-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 128.5°-159.5° C.

NMR (D₂ O, δ): 0.63 (3H, t, J=7.5 Hz), 1.01-1.24 (2H, m), 1.31-1.53 (2H,m), 2.43 (3H, s), 2.74 (2H, t, J=7.5 Hz), 5.38 (2H, s), 6.28 (1H, t,J=3.0 Hz), 6.55 (1H, br s), 6.71-6.81 (1H, m), 6.90 (1H, d, J=5.0 Hz),7.00 (1H, d, J=8.0 Hz), 7.09 (1H, d, J=8.0 Hz), 7.21 (1H, s), 7.95 (1H,d, J=5.0 Hz)

(7) Sodium salt of3-[3-bromo-4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 159.5°-170.5° C.

NMR (D₂ O, δ): 0.52 (3H, t, J=7.5 Hz), 0.92-1.18 (2H, m), 1.27-1.50 (2H,m), 2.36 (3H, s), 2.69 (2H, t, J=7.5 Hz), 5.35 (2H, s), 6.30 (1H, d,J=1.0 Hz), 6.66 (1H, d, J=1.0 Hz), 6.79 (1H, d, J=5.0 Hz), 6.98 (2H, s),7.17 (1H, s), 7.89 (1H, d, J=5.0 Hz)

(8) Sodium salt of3-[4-[2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]-3-chlorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 165°-175° C.

NMR (D₂ O, δ): 0.47 (3H, t, J=7 Hz), 0.98 (2H, m), 1.27 (2H, m), 2.69(2H, t, J=8 Hz), 5.36 (2H, br s), 6.20 (1H, d, J=4 Hz), 6.72 (1H, d, J=4Hz), 6.82 (1H, d, J=5 Hz), 6.94 (1H, dd, J=8 Hz & 1 Hz), 6.99 (1H, d,J=8 Hz), 7.10 (1H, s), 7.94 (1H, d, J=5 Hz)

(9) Sodium salt of3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]-3-chlorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 168°-178° C.

NMR (D₂ O, δ): 0.61 (3H, t, J=7.5 Hz), 1.13 (2H, m), 1.42 (2H, m), 2.43(3H, s), 2.73 (2H, t, J=8 Hz), 5.49 (2H, s), 6.43 (1H, d, J=1 Hz), 6.68(1H, d, J=1 Hz), 6.90 (1H, d, J=5 Hz), 6.91-7.08 (3H, m), 7.94 (1H, d,J=5 Hz)

(10) Sodium salt of3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]-2-chlorobenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.60 (3H, t, J=7.5 Hz), 1.07 (2H, m), 1.37 (2H, m), 2.39(3H, s), 2.60 (2H, t, J=8 Hz), 5.30 (2H, br s), 6.20 (1H, d, J=9 Hz),6.42 (1H, dd, J=9 Hz & 1 Hz), 6.45 (1H, d, J=1 Hz), 6.55 (1H, d, J=1Hz), 6.84 (1H, d, J=5 Hz), 6.95 (1H, d, J=1 Hz), 7.86 (1H, d, J=5 Hz)

(11) Sodium salt of3-[4-[2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.65 (3H, t, J=7.5 Hz), 1.36 (2H, m), 2.41 (3H, s), 2.69(2H, t, J=8 Hz), 5.37 (2H, s), 6.27 (1H, d, J=4 Hz), 6.66 (1H, d, J=4Hz), 6.81 (2H, d, J=8 Hz), 6.90 (1H, d, J=5 Hz), 6.94 (2H, d, J=8 Hz),7.94 (1H, d, J=5 Hz)

(12) Sodium salt of2-butyl-7-methyl-3-[3-nitro-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.72 (3H, t, J=7 Hz), 1.22 (2H, m), 1.50 (2H, m), 2.83(2H, t, J=7 Hz), 5.52 (2H, s), 6.39 (1H, t, J=3 Hz), 6.76 (1H, dd, J=3Hz & 1 Hz), 6.83 (1H, d, J=1 Hz), 7.00 (1H, d, J=5 Hz), 7.28-7.42 (2H,m), 7.62 (1H, s), 8.00 (1H, d, J=5 Hz)

(13) Sodium salt of2-butyl-3-[3-chloro-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 49°-50° C.

NMR (D₂ O, δ): 0.62 (3H, t, J=7.5 Hz), 1.10 (2H, m), 1.40 (2H, m), 2.43(3H, s), 2.71 (2H, t, J=8 Hz), 5.34 (2H, s), 6.27 (1H, t, J=3 Hz), 6.52(1H, br s), 6.73 (1H, d, J=4 Hz), 6.83 (1H, d, J=5 Hz), 6.90 (1H, d, J=8Hz), 7.00 (2H, m), 7.90 (1H, d, J=5 Hz)

(14) Potassium salt of3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.69 (3H, t, J=7.5 Hz), 1.43 (2H, m), 2.60 (2H, t, J=7.5Hz), 5.74 (2H, s), 6.26 (1H, d, J=1 Hz), 6.52 (2H, d, J=9 Hz), 6.55 (1H,d, J=1 Hz), 6.71 (1H, d, J=5 Hz), 6.73 (1H, d, J=5 Hz), 7.82 (1H, d, J=5Hz)

EXAMPLE 7

The following compounds were obtained according to similar manners tothose of Example 1 and Example 3, successively.

(1) Sodium salt of3-[4-[4-bromo-3-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 160°-175° C.

NMR (D₂ O, δ): 0.43 (3H, t, J=7 Hz), 0.94 (2H, m), 1.27 (2H, m), 2.66(2H, t, J=7 Hz), 5.43 (2H, s), 6.63 (1H, s), 6.76 (2H, d, J=9 Hz), 6.83(1H, d, J=5 Hz), 6.97 (2H, d, J=9 Hz), 7.96 (1H, d, J=5 Hz)

(2) Sodium salt of3-[4-(2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]-2-methoxybenzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.51 (3H, t, J=7 Hz), 1.00 (2H, m), 1.28 (2H, m), 2.38(3H, s), 2.57 (2H, t, J=7 Hz), 3.52 (3H, s), 5.20 (2H, s), 6.15 (1H, d,J=2 Hz), 6.28 (1H, d, J=8 Hz), 6.41 (1H, d, J=8 Hz), 6.59 (1H, d, J=2Hz), 6.66 (1H, s), 6.82 (1H, d, J=4 Hz), 7.92 (1H, d, J=4 Hz)

EXAMPLE 8

A mixture of2-butyl-7-methyl-3-[3-nitro-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine(145 mg), 10% palladium on carbon (30 mg), and methanol (5 ml) wasstirred at room temperature for 5 hours under hydrogen atmosphere (4atom). After vacuum filtration, the filtrate was evaporated in vacuo togive a yellow residue of3-[3-amino-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine(130 mg). This residue was treated with acetic anhydride (1 ml) andpyridine (2 ml) at room temperature for 2 hours. The reaction mixturewas evaporated in vacuo and purified by preparative thin layerchromatography (ethyl acetate-acetic acid=19:1) to give a brownishviscous oil (65 ml). To a solution of the oil in ethanol (2 ml) wasadded a solution of sodium hydrogencarbonate (12.8 mg) in water (1 ml)and the mixture was evaporated in vacuo. The residue was dissolved inwater (2 ml) and lyophilized to afford sodium salt of3-[3-acetamido-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine(65 mg) as an amorphous powder.

NMR (D₂ O, δ): 0.79 (3H, t, J=7 Hz), 1.28 (2H, m), 1.56 (2H, m), 1.74(3H, s), 2.55 (3H, s), 2.87 (2H, t, J=7 Hz), 5.49 (2H, s), 6.41 (1H, brs), 6.73 (1H, br s), 6.81 (1H, br s), 6.96 (1H, d, J=8 Hz), 7.08 (1H, d,J=5 Hz), 7.19 (1H, br s), 7.21 (1H, d, J=8 Hz), 8.08 (1H, d, J=5 Hz)

EXAMPLE 9

The following compounds were obtained according to a similar manner tothat of Example 1.

(1)2-Butyl-3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 186°-190.5° C.

NMR (CD₃ OD-CDCl₃, δ): 0.91 (3H, t, J=7.5 Hz), 1.31-1.52 (2H, m),1.64-1.83 (2H, m), 2.70 (3H, s), 2.91 (2H, t, J=7.5 Hz), 5.58 (2H, s),6.85 (1H, d, J=1.5 Hz), 6.98 (1H, d, J=1.5 Hz), 7.14 (1H, d, J=5.0 Hz),7.19 (4H, s), 8.21 (1H, d, J=5.0 Hz)

(2)3-[4-[4-Chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 225°-227° C.

NMR (DMSO-d₆, δ): 0.95 (3H, t, J=7.5 Hz), 1.62-1.86 (2H, m), 2.57 (3H,s), 2.84 (2H, t, J=7.5 Hz), 5.58 (2H, s), 6.92 (1H, d, J=1 Hz), 7.10(1H, d, J=5 Hz), 7.14-7.35 (4H, m), 7.49 (1H, d, J=1 Hz), 8.18 (1H, d,J=5 Hz)

EXAMPLE 10

The following compounds were obtained according to a similar manner tothat of Example 3.

(1) Sodium salt of2-butyl-3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 161°-170° C.

NMR (D₂ O, δ): 0.68 (3H, t, J=7.5 Hz), 1.02-1.23 (2H, m), 1.31-1.50 (2H,m), 2.44 (3H, s), 2.67 (2H, t, J=7.5 Hz), 5.31 (2H, s), 6.51 (1H, d,J=1.0 Hz), 6.57 (1H, d, J=1.0 Hz), 6.65 (2H, d, J=8.5 Hz), 6.82 (2H, d,J=8.5 Hz), 6.90 (1H, d, J=5.0 Hz), 7.92 (1H, d, J=5.0 Hz)

(2) Sodium salt of3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 184°-187° C.

NMR (D₂ O, δ): 0.74 (3H, t, J=7.5 Hz), 1.35-1.59 (2H, m), 2.42 (3H, s),2.65 (2H, t, J=7.5 Hz), 5.30 (2H, s), 6.44 (1H, d, J=1 Hz), 6.51-6.63(3H, m), 6.77 (2H, d, J=8 Hz), 6.86 (1H, d, J=5 Hz), 7.39 (1H, d, J=5Hz)

EXAMPLE 11

The following compounds were obtained according to a similar manner tothat of Example 1.

(1)2-Butyl-3-[3-fluoro-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 106.5°-108° C.

NMR (DMSO-d₆, δ): 0.89 (3H, t, J=7.5 Hz), 1.27-1.50 (2H, m), 1.62-1.81(2H, m), 2.57 (3H, s), 2.89 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.46 (1H,t, J=3.0 Hz), 6.94-7.04 (2H, m), 7.11 (1H, d, J=5.0 Hz), 7.17-7.29 (2H,m), 7.41 (1H, t, J=8.5 Hz), 8.18 (1H, d, J=5.0 Hz)

(2)2-Butyl-3-[4-[2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]-2-fluorobenzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.85 (3H, t, J=7.5 Hz), 1.25-1.47 (2H, m), 1.59-1.78(2H, m), 2.57 (3H, s), 2.86 (2H, t, J=7.5 Hz), 5.62 (2H, s), 6.58 (1H,d, J=4.5 Hz), 6.89-7.16 (2H, m), 6.93 (1H, d, J=4.5 Hz), 7.10 (1H, d,J=5.0 Hz), 7.40 (1H, dd, J=10.0 Hz & 1.0 Hz), 8.18 (1H, d, J=5.0 Hz)

(3)3-[[2-[4-Bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]pyridin-5-yl]methyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.88 (3H, t, J=7.5 Hz), 1.27-1.49 (2H, m), 1.61-1.80(2H, m), 2.55 (3H, s), 2.90 (2H, t, J=7.5 Hz), 5.56 (2H, s), 6.72 (1H,d, J=1.5 Hz), 7.09 (1H, d, J=5.0 Hz), 7.17 (1H, d, J=8.5 Hz), 7.58 (1H,d, J=1.5 Hz), 7.60 (1H, dd, J=8.5 Hz & 1.0 Hz), 8.15 (1H, d, J=5.0 Hz),8.31 (1H, d, J=1.0 Hz)

(4)3-[3-Bromo-4-[2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.83 (3H, t, J=7.5 Hz), 1.25-1.45 (2H, m), 1.56-1.72(2H, m), 2.58 (3H, s), 2.88 (2H, t, J=7.5 Hz), 5.63 (2H, s), 6.62 (1H,d, J=4.5 Hz), 7.01 (1H, d, J=4.5 Hz), 7.12 (1H, d, J=5.0 Hz), 7.18 (1H,dd, J=8.5 Hz & 1.0 Hz), 7.42 (1H, d, J=8.5 Hz), 7.69 (1H, d, J=1.0 Hz),8.19 (1H, d, J=5.0 Hz)

(5)2-Butyl-3-[4-[2-cyano-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.87 (3H, t, J=7.5 Hz), 1.22-1.45 (2H, m), 1.57-1.76(2H, m), 2.57 (3H, s), 2.83 (2H, t, J=7.5 Hz), 5.58 (2H, s), 6.58 (1H,d, J=4 Hz), 7.06-7.33 (6H, m), 8.18 (1H, d, J=5 Hz)

(6)7-Methyl-2-propyl-3-[4-[2-(1H-tetrazol-5-yl)-4-vinyl-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ +CD₃ OD, δ): 0.92 (3H, t, J=7.5 Hz), 1.59-1.82 (2H, m), 2.60(3H, s), 2.72 (2H, t, J=7.5 Hz), 4.96 (1H, dd, J=l1 Hz & 1 Hz),5.32-5.50 (3H, m), 6.50 (1H, dd, J=l1 Hz, 17.5 Hz), 6.83-6.90 (2H, m),6.89-7.08 (5H, m), 8.05 (1H, d, J=5 Hz)

EXAMPLE 12

A mixture of7-methyl-2-propyl-3-[4-[2-(1H-tetrazol-5-yl)-4-vinyl-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine(40 mg), 10% palladium on carbon (10 mg) and methanol (5 ml) was stirredat room temperature for 4 hours under hydrogen atmosphere (3 atm). Afterfiltration, the filtrate was evaporated in vacuo. The residue waspurified by preparative thin layer chromatography(dichloromethane:methanol=5:1) to give3-[4-[4-ethyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine(20 ml).

NMR (CDCl₃, +CD₃ OD, δ): 0.99 (3H, t, J=7.5 Hz), 1.21 (3H, t, J=7.5 Hz),1.64-1.87 (2H, m), 2.44-2 60 (2H, m), 2.64 (3H, s), 2.80 (2H, t, J=7.5Hz), 5.46 (2H, s), 6.67-6.76 (2H, m), 6.97-7.13 (5H, m), 8.13 (1H, d,J=5 Hz)

EXAMPLE 13

A mixture of3-[4-(2-cyano-1-pyrrolyl)-3-methylbenzyl]-7-methyl-3-propyl-3H-imidazo[4,5-b]pyridine(260 mg), sodium azide (183 mg), triethylamine hydrochloride (484 mg)and 1,3-dimethyl-2-imidazolidinone (5 ml) were stirred at 130° C. for 2days under nitrogen atmosphere. The mixture was poured into water (25ml) and the pH value was adjusted to 4 with 7% hydrochloric acid. Themixture was extracted with ethyl acetate and the organic layer waswashed with brine, dried over magnesium sulfate and evaporated in vacuo.The residue was purified by preparative thin layer chromatography (CH₂Cl₂ -MeOH=6:1) to afford7-methyl-3-[3-methyl-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine(225 mg).

NMR (CDCl₃, δ): 0.96 (3H, t, J=7.5 Hz), 1.67-2.00 (5H, m), 2.72 (3H, s),2.98 (2H, t, J=7.5 Hz), 5.54 (2H, s), 6.36-6.43 (1H, m), 6.77-6.84 (1H,m), 6.93-7.22 (5H, m), 8.29 (1H, d, J=5 Hz)

EXAMPLE 14

The following compounds were obtained according to a similar manner tothat of Example 13.

(1)1-[4-[4-Bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-6-ethoxycarbonyl-1H-benzimidazole

NMR (CD₃ OD, δ): 0.91 (3H, t, J=7.5 Hz), 1.23-1.53 (5H, m), 1.65-1.86(2H, m), 2.92 (2H, t, J=7.5 Hz), 4.35 (2H, q, J=7.5 Hz), 5.59 (2H, s),6.65 (1H, d, J=1 Hz), 7.01-7.20 (5H, m), 7.69 (1H, d, J=8 Hz), 7.95 (1H,dd, J=8 Hz & 1 Hz), 8.10 (1H, d, J=1 Hz)

(2)3-[4-[4-Bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-5-methoxy-3H-imidazo[4,5-b]pyridine

mp: 235°-241° C.

NMR (CDCl₃, +CD₃ OD, δ): 0.92 (3H, t, J=7.5 Hz), 1.38-1.51 (2H, m),1.63-1.85 (2H, m), 2.75-2.90 (2H, t-like, J=7.5 Hz), 3.98 (3H, s), 5.48(2H, s), 6.72 (1H, d, J=9 Hz), 6.91 (1H, d, J=1 Hz), 7.01 (1H, d, J=1Hz), 7.15-7.32 (4H, m), 7.89 (1H, d, J=9 Hz)

(3)2-Butyl-3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.82 (3H, t, J=7.5 Hz), 1.19-1.46 (2H, m), 1.59-1.81(2H, m), 2.78 (2H, t, J=7.5 Hz), 5.48 (2H, s), 6.83-7.0 (2H, m),7.00-7.38 (5H, m), 7.98 (2H, d, J=8 Hz), 8.37 (2H, d, J=5 Hz)

EXAMPLE 15

The following compounds were obtained according to a similar manner tothat of Example 3.

(1) Sodium salt of2-butyl-3-[3-fluoro-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 93°-131° C.

NMR (D₂ O, δ): 0.66 (3H, t, J=7.5 Hz), 1.03-1.25 (2H, m), 1.32-1.52 (2H,m), 2.45 (3H, s), 2.72 (2H, t, J=7.5 Hz), 5.35 (2H, s), 6.32 (1H, t,J=3.5 Hz), 6.63-6.90 (4H, m), 6.89 (1H, d, J=5.0 Hz), 6.94 (1H, t, J=8.0Hz), 7.91 (1H, d, J=5.0 Hz)

(2) Sodium salt of2-butyl-3-[4-[2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]-2-fluorobenzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 129°-151° C.

NMR (D₂ O, δ): 0.52 (3H, t, J=7.5 Hz), 0.90-1.12 (2H, m), 1.20-1.41 (2H,m), 2.32 (3H, s), 2.65 (2H, t, J=7.5 Hz), 5.37 (2H, s), 6.11 (1H, d,J=4.0 Hz), 6.50 (1H, d, J=8.0 Hz), 6.61 (1H, d, J=4.0 Hz), 6.68 (1H, d,J=8.0 Hz), 6.75-6.87 (2H, m), 7.91 (1H, d, J=5.0 Hz)

(3) Sodium salt of3-[[2-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]pyridin-5-yl]methyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 155°-170.5° C.

NMR (D₂ O, δ): 0.72 (3H, t, J=7.5 Hz), 1.09-1.33 (2H, m), 1.40-1.58 (2H,m), 2.48 (3H, s), 2.81 (2H, t, J=7.5 Hz), 5.43 (2H, s), 6.61 (1H, d,J=9.0 Hz), 6.64 (1H, d, J=1.5 Hz), 6.95 (1H, d, J=5.0 Hz), 6.97 (1H, d,J=1.5 Hz), 7.30 (1H, dd, J=9.0 Hz & 1.0 Hz), 7.93 (1H, d, J=5.0 Hz),8.13 (1H, d, J=1.0 Hz)

(4) Sodium salt of3-[3-bromo-4-[2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 142°-169° C.

NMR (D₂ O, δ): 0.50 (3H, t, J=7.5 Hz), 0.89-1.11 (2H, m), 1.21-1.42 (2H,m), 2.38 (3H, s), 2.70 (2H, t, J=7.5 Hz), 5.39 (2H, s), 6.21 (1H, d,J=4.5 Hz), 6.72 (1H, d, J=4.5 Hz), 6.84 (1H, d, J=5.0 Hz), 7.04 (2H, s),7.29 (1H, s), 7.97 (1H, d, J=5.0 Hz)

(5) Sodium salt of2-butyl-3-[4-[2-cyano-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.60 (3H, t, J=7.5 Hz), 0.97-1.20 (2H, m), 1.20-1.41(2H, m), 2.44 (3H, s), 2.71 (2H, t, J=7.5 Hz), 5.38 (2H, s), 6.72 (1H,d, J=4 Hz), 6.88-7.08 (6H, m), 7.97 (1H, d, J=5 Hz)

(6) Sodium salt of7-methyl-3-[3-methyl-4-[2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 125°-128° C.

NMR (D₂ O, δ): 0.80 (3H, t, J=7.5 Hz), 1.40-1.70 (5H, m), 2.51 (3H, s),2.77 (2H, t, J=7.5 Hz), 5.38 (2H, s), 6.32-6.41 (1H, m), 6.59-6.68 (1H,m), 6.68-6.82 (2H, m), 6.82-6.96 (2H, m), 7.00 (1H, d, J=5 Hz), 8.01(1H, d, J=5 Hz)

(7) Sodium salt of2-butyl-3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 190°-193° C.

NMR (D₂ O, δ): 0.62 (3H, t, J=7.5 Hz), 0.96-1.19 (2H, m), 1.32-1.56 (2H,m), 2.60 (2H, t, J=7.5 Hz), 5.30 (2H, s), 6.41 (1H, d, J=2 Hz), 6.52(1H, d, J=2 Hz), 6.62 (2H, d, J=8 Hz), 6.82 (2 H, d, J=8 Hz), 7.10 (1H,dd, J=5 Hz & 8 Hz), 7.85 (1H, dd, J=8 Hz & 1 Hz), 8.06 (1H, dd, J=5 Hz &1 Hz)

(8) Sodium salt of7-methyl-2-propyl-3-[4-[2-(1H-tetrazol-5-yl)-4-vinyl-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.79 (3H, t, J=7.5 Hz), 1.40-1.64 (2H, m), 2.52 (3H, s),2.63-2.85 (2H, m), 5.00-5.12 (1H, m), 5.32-5.60 (3H, m), 6.42-7.14 (8H,m), 7.92-8.05 (1H, m)

(9) Sodium salt of3-[4-[4-ethyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.84 (3H, t, J=7.5 Hz), 1.17 (3H, t, J=7.5 Hz), 1.50-1.70(2H, m), 2.39-2.64 (5H, m), 2.70-2.87 (2H, m), 5.48 (2H, s), 6.58-6.70(2H, m), 6.83 (2H, d, J=8 Hz), 6.94 (2H, d, J=8 Hz), 7.12 (1H, d, J=5Hz), 8.08 (1H, d, J=5 Hz)

EXAMPLE 16

The following compounds were obtained according to similar manners tothose of Examples 1 and 3, successively.

(1) Sodium salt of3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-3H-imidazo[4,5-d]pyrimidine

NMR (D₂ O, δ): 0.60 (3H, t, J=7.5 Hz), 0.93-1.21 (2H, m), 1.32-1.58 (2H,m), 2.65 (2H, t, J=7.5 Hz), 5.31 (2H, s), 6.39 (1H, d, J=1 Hz), 6.48(1H, d, J=1 Hz), 6.70 (2H, d, J=8 Hz), 6.91 (2H, d, J=8 Hz), 8.69 (1H,s), 8.82 (1H, s)

(2) Sodium salt of1-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butylthieno[3,4-d]imidazole

NMR (D₂ O, δ): 0.72 (3H, t, J=7 Hz), 1.19 (2H, m), 1.50 (2H, m), 2.60(2H, t, J=7 Hz}, 4.95 (2H, s), 6.00 (1H, s), 6.44 (1H, s), 6.64 (2H, d,J=9 Hz), 6.80 (2H, d, J=9 Hz)

(3) Sodium salt of 1-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-4-chloro-5-hydroxymethylimidazole

NMR (D₂ O, δ): 0.69 (3H, t, J=7 Hz), 1.11 (2H, m), 1.40 (2H, m), 2.47(2H, t, J=7 Hz), 4.43 (2H, s). 5.20 (2H, s), 6.69 (1H, d, J=2 Hz), 6.77(1H, d, J=2 Hz), 6.86 (4H, s)

EXAMPLE 17

The following compounds were obtained according to similar manners tothose of Examples 13 and 3, successively.

(1) Sodium salt of3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-5-chloro-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.63 (3H, t, J=7.5 Hz), 0.94-1.19 (2H, m), 1.33-1.55 (2H,m), 2.61 (2H, t, J=7.5 Hz), 5.20 (2H, s), 6.38 (1H, d, J=1 Hz), 6.57(1H, d, J=1 Hz), 6.68 (2H, d, J=8 Hz), 6.84 (2H, d, J=8 Hz), 6.93 (1H,d, J=8 Hz), 7.69 (1H, d, J=8 Hz)

(2) Sodium salt of2-butyl-3-[4-[4-tert-butyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 188°-195° C.

NMR (D₂ O, δ): 0.61 (3H, t, J=7.5 Hz), 0.85-1.18 (11H, m), 1.30-1.50(2H, m), 2.44 (3H, s), 2.63 (2H, t), 5.31 (2H, s), 6.38 (1H, d), 6.57(1H, d), 6.68 (2H, d, J=8 Hz), 6.84 (2H, d, J=8 Hz), 6.92 (1H, d, J=5Hz), 7.93 (1H, d, J=5 Hz)

EXAMPLE 18

The following compounds were obtained according to a similar manner tothat of Example 1.

(1) A mixture of3-[4-[2-bromo-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridineand3-[4-[2-bromo-1-methyl-3-(1H-tetrazol-5-yl)-4-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine.

NMR (DMSO-d₆, δ): 0.93 (3H, t, J=7.5 Hz), 1.61-1.86 (2H, m), 2.57 (3H,s), 2.83 (2H, t, J=7.5 Hz), 3.70 (3H, s), 5.51 (2H, s), 7.05-7.26 (5H,m), 7.51 (1H, s), 8.16 (1H, d, J=5 Hz)

(2)3-[4-[1-Methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ +CD₃ OD, δ): 1.02 (3H, t, J=7.5 Hz), 1.71-1.93 (2H, m), 2.91(2H, t, J=7.5 Hz), 2.65 (3H, s), 2.91 (2H, t, J=7.5 Hz), 3.75 (3H, s),5.51 (2H, s), 6.72 (1H, d, J=2 Hz), 7.03 (2H, d, J=9 Hz), 7.11 (1H, d,J=5 Hz), 7.20 (2H, d, J=9 Hz), 7.33 (1H, d, J=2 Hz), 8.19 (1H, d, J=5Hz)

EXAMPLE 19

The following compounds were obtained according to a similar manner tothat of Example 3.

(1) A mixture of sodium salt of3-[4-[2-bromo-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridineand sodium salt of3-[4-[2-bromo-1-methyl-3-(1H-tetrazol-5-yl)-4-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine.

mp: 83°-85° C.

NMR (D₂ O, δ): 0.63 (3H, t, J=7.5 Hz), 1.27-1.52 (2H, m), 2.31 (3H, s),2.59 (2H, t, J=7.5 Hz), 3.23 (3H, s), 5.24 (2H, s), 6.67-6.90 (5H, m),7.18 (1H, s), 7.88 (1H, d, J=5 Hz)

(2) Sodium salt of3-[4-[1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 140°-143° C.

NMR (D₂ O, δ): 0.78 (3H, t, J=7.5 Hz), 1.40-1.65 (2H, m), 2.48 (3H, s),2.64 (2H, t, J=7.5 Hz), 3.58 (3H, s), 5.28 (2H, s), 6.52 (1H, d, J=2Hz), 6.73 (2H, d, J=9 Hz), 6.88 (2H, d, J=9 Hz), 6.99 (1H, d, J=5 Hz),7.05 (1H, d, J=2 Hz), 7.97 (1H, d, J=5 Hz)

EXAMPLE 20

The following compounds were obtained according to a similar manner tothat of Example 1.

(1)7-Methyl-3-[4-[4-methyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.93 (3H, t, J=7.5 Hz), 1.62-1.84 (2H, m), 2.09 (3H,s), 2.56 (3H, s), 2.83 (2H, t, J=7.5 Hz), 5.52 (2H, s), 6.67 (1H, d,J=1.0 Hz), 6.99 (1H, d, J=1.0 Hz), 7.09 (1H, d, J=5.0 Hz), 7.18 (4H, s),8.18 (1H, d, J=5.0 Hz)

(2)7-Methyl-3-[4-[5-methylthio-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 181°-183° C.

NMR (DMSO-d₆, δ): 0.91 (3H, t, J=7.5 Hz), 1.57-1.78 (2H, m), 2.18 (3H,s), 2.57 (3H, s), 2.81 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.51 (1H, d, J=5Hz), 6.91 (1H, d, J=5 Hz), 7.22 (4H, s-like), 8.19 (1H, d, J=5 Hz)

(3)3-[4-[4-Chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidzo[4,5-b]pyridine

NMR (CDCl₃, δ): 1.31 (3H, t, J=7.5 Hz), 2.60 (3H, s), 2.62 (3H, s), 2.81(2H, q, J=7.5 Hz), 5.50 (2H, s), 6.83 (1H, d, J=1 Hz), 6.90-6.98 (2H,m), 7.03-7.20 (4H, m)

EXAMPLE 21

The following compounds were obtained according to a similar manner tothat of Example 13.

(1) 7-Methyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 184°-186° C.

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=7.5 Hz), 1.57-1.79 (2H, m), 1.99 (3H,s), 2.57 (3H, s), 2.82 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.18 (1H, d,J=4.5 Hz), 6.80 (1H, d, J=4.5 Hz), 7.10 (1H, d, J=5.0 Hz), 7.22 (4H, s),8.19 (1H, d, J=5.0 Hz)

(2)3-[4-[3-Chloro-2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 190.5°-192.5° C.

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=7.5 Hz), 1.56-1.79 (2H, m), 1.98 (3H,s), 2.57 (3H, s), 2.82 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.90 (1H, s),7.11 (1H, d, J=5.0 Hz), 7.24 (4H, s), 8.18 (1H, d, J=5.0 Hz)

EXAMPLE 22

The following compounds were obtained according to a similar manner tothat of Example 3.

(1) Sodium salt of7-methyl-3-[4-[4-methyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.74 (3H, t, J=7.5 Hz), 1.35-1.58 (2H, m), 1.97 (3H, s),2.43 (3H, s), 2.63 (2H, t, J=7.5 Hz), 5.26 (2H, s), 6.25 (1H, d, J=1.0Hz), 6.51 (1H, d, J=1.0 Hz), 6.58 (2H, d, J=9.0 Hz), 6.73 (2H, d, J=9.0Hz), 6.87 (1H, d, J=5.0 Hz), 7.89 (1H, d, J=5.0 Hz)

(2) Sodium salt of7-methyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.66 (3H, t, J=7.5 Hz), 1.23-1.48 (2H, m), 1.62 (3H, s),2.35 (3H, s), 2.65 (2H, t, J=7.5 Hz), 5.27 (2H, s), 5.97 (1H, d, J=4.5Hz), 6.59 (1H, d, J=4.5 Hz), 6.71 (2H, d, J=9.0 Hz), 6.76 (1H, d, J=5.0Hz), 6.89 (2H, d, J=9.0 Hz), 7.85 (1H, d, J=5.0 Hz)

(3) Sodium salt of3-[4-[3-chloro-2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.57 (3H, t, J=7.5 Hz), 1.22-1.48 (2H, m), 1.36 (3H, s),2.29 (3H, s), 2.61 (2H, t, J=7.5 Hz), 5.27 (2H, s), 6.48 (1H, s), 6.58(2H, d, J=9.0 Hz), 6.71 (1H, d, J=5.0 Hz), 6.87 (2H, d, J=9.0 Hz), 7.82(1H, d, J=5.0 Hz)

(4) Sodium salt of7-methyl-3-[4-[5-methylthio-2-[1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.68 (3H, t, J=7.5 Hz), 1.25-1.55 (2H, m), 1.79 (3H, s),2.40 (3H, s), 2.69 (3H, t, J=7.5 Hz), 5.38 (2H, s), 6.35 (1H, d, J=5Hz), 6.68 (1H, d, J=5 Hz), 6.85 (2H, d, J=8 Hz), 6.95 (2H, d, J=8 Hz),7.93 (1H, d, J=5 Hz)

(5) Sodium salt of 3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 1.13 (3H, t, J=7.5 Hz), 2.39 (3H, s), 2.42 (3H, s), 2.72(2H, q, J=7.5 Hz), 5.38 (2H, s), 6.59-6.67 (2H, m), 6.70 (2H, d, J=8Hz), 6.81-6.93 (3H, m)

EXAMPLE 23

The following compound was obtained according to similar manners tothose of Examples 1 and 3, successively.

Sodium salt of2-butyl-7-methyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.69 (3H, t, J=7 Hz), 1.16 (2H, m), 1.40 (2H, m), 1.88(3H, s), 2.50 (3H, s), 2.78 (2H, t, J=7 Hz), 5.43 (2H, s), 6.11 (1H, d,J=4 Hz), 6.60 (1H, d, J=4 Hz), 6.90 (2H, d, J=8 Hz), 7.00 (2H, d, J=8Hz), 7.03 (1H, d, J=5 Hz), 8.03 (1H, d, J=5 Hz)

EXAMPLE 24

A mixture of trimethyltin azide (315 mg) and2-cyano-4-difluoromethyl-1-pyrrolyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine(155.3 mg) in xylene (3 ml) was stirred at 125° C. for 16 hours andconcentrated in vacuo. The residue was dissolved in methanol (2 ml) andthe methanolic solution was treated with aqueous 8.9N-hydrochloric acid(0.3 ml). The solution was adjusted to pH 5 with aqueous 1N sodiumhydroxide solution and then concentrated in vacuo. The residue waspurified by preparative thin layer chromatography to yield3-[4-[4-formyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine (60 mg) as an amorphous solid.

NMR (CDCl₃, δ): 0.93 (3H, t, J=7.5 Hz), 1.63-1.87 (2H, m), 2.57 (3H, s),2.82 (2H, t, J-7.5 Hz), 5.54 (2H, s), 6.90 (1H, d, J=1 Hz), 7.09 (1H, d,J=5 Hz), 7.17 (2H, d, J=8 Hz), 7.25 (2H, d, J=8 Hz), 7.93 (1H, d, J=1Hz), 8.16 (1H, d, J=5 Hz), 9.78 (1H, s)

EXAMPLE 25

The following compound was obtained according to similar manners tothose of Preparation 55 and Example 3, successively.

Sodium salt of3-[4-[4-hydroxymethyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.81 (3H, t, J=7.5 Hz), 1.44-1.68 (2H, m), 2.56 (3H, s),2.76 (2H, t, J=7.5 Hz), 4.56 (2H, s), 5.44 (2H, s), 6.72 (1H, d, J=1Hz), 6.76-6.94 (5H, m), 7.09 (1H, d, J=5 Hz), 8.03 (1H, d, J=5 Hz)

EXAMPLE 26

To a suspension of3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine(10.33 g) in ethanol (100 ml) was added concentrated hydrochloric acid(10 ml) and ethanol (200 ml). The mixture was heated to 40°-50° C. in awater bath. The resulting solution was concentrated to half volume underreduced pressure. The precipitates were collected by filtration, washedwith ethanol (50 ml) and dried over phosphorus pentoxide to yield3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridinehydrochloride (7.70 g) as a cream powder.

mp: 140°-143° C.

NMR (DMSO-d₆, δ): 0.98 (3H, t, J=7.5 Hz), 1.76 (2H, m), 2.71 (3H, s),3.19 (2H, t, J=7.5 Hz), 5.78 (2H, s), 7.02 (1H, d, J=1 Hz), 7.29 and7.40 (4H, ABq, J=8.5 Hz), 7.42-7.48 (3H, m), 8.48 (1H, d, J=5 Hz)

EXAMPLE 27

The following compounds were obtained according to a similar manner tothat of Example 1.

(1)7-Methyl-2-propyl-3-[4-[2-(1H-tetrazol-5-yl)-4-trifluoromethyl-1-pyrrolyl]benzyl]-3H-imiazo[4,5-b]piridine

NMR (DMSO-d₆, δ): 0.96 (3H, t, J=7 Hz), 1.76 (2H, dt, J=7 Hz, 7 Hz),2.57 (3H, s), 2.85 (2H, t, J=7 Hz), 5.57 (2H, s), 7.08 (1H, s), 7.21(2H, d, J=8 Hz), 7.31 (2H, d, J=8 Hz), 7.85 (1H, s), 8.18 (1H, d, J=5Hz)

(2)5,7-Dimethyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidzo[4,5-b]pyridine

mp: 242°-243° C.

NMR (DMSO-d₆, δ): 0.88 (3H, t, J=7 Hz), 1.65 (2H, dt, J=7 Hz, 7 Hz),2.00 (3H, s), 2.52 (3H, s), 2.53 (3H, s), 2.76 (2H, t, J=7 Hz), 5.56(2H, s), 6.18 (1H, d, J=4 Hz), 6.80 (1H, d, J=4 Hz), 6.97 (1H, s), 7.21(4H, s)

(3)3-[4-[2,3-Dimethyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 212°-215° C.

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=7.5 Hz), 1.58-1.80 (2H, m), 1.91 (3H,s), 2.06 (3H, s), 2.57 (3H, s), 2.82 (2H, t, J=7.5 Hz), 5.60 (2H, s),6.70 (1H, s), 7.10 (1H, d, J=5.0 Hz), 7.18 (2H, d, J=9.0 Hz), 7.24 (2H,d, J=9.0 Hz), 8.20 (1H, d, J=5.0 Hz)

(4)3-[4-[2-Chloro-3-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 213°-215° C.

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=7.5 Hz), 1.59-1.81 (2H, m), 2.10 (3H,s), 2.57 (3H, s), 2.82 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.85 (1H, s),7.10 (1H, d, J=5.0 Hz), 7.23 (4H, s), 8.18 (1H, d, J=5.0 Hz)

(5)3-[4-[2-Bromo-3-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 214°-216° C.

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=7.5 Hz), 1.58-1.80 (2H, m), 2.08 (3H,s), 2.57 (3H, s), 2.81 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.85 (1H, s),7.11 (1H, d, J=5 Hz), 7.16-7.30 (4H, m), 8.19 (1H, d, J=5 Hz)

(6)2-Ethyl-5,7-dimethyl-3-[4-[5-methyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 261°-263° C.

NMR (DMSO-d₆, δ): 1.20 (3H, t, J=7 Hz), 2.00 (3H, s), 2.52 (3H x 2, s),2.79 (2H, q, J=7 Hz), 5.55 (2H, s), 6.18 (1H, d, J=4 Hz), 6.81 (1H, d,J=4 Hz), 6.96 (1H, s), 7.20 (4H, s)

(7)3-[4-[4-Chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-ethyl-7-methyl-3H-imidazo[4,5-b]pyridine

mp: 210°-213° C.

NMR (DMSO-d₆, δ): 1.29 (3H, t, J=8 Hz), 2.57 (3H, s), 2.87 (2H, t, J=8Hz), 5.53 (2H, s), 6.89 (1H, d, J=2 Hz), 7.09 (1H, d, J=4 Hz), 7.20 (2H,d, J=7 Hz), 7.24 (2H, d, J=7 Hz), 7.46 (1H, d, J=2 Hz), 8.18 (1H, d, J=4Hz)

(8)3-[4-[4-Chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.96 (3H, t, J=7.5 Hz), 1.65-1.88 (2H, m), 2.85 (2H,t, J=7.5 Hz), 5.59 (2H, s), 6.89 (1H, d, J=1 Hz), 7.15-7.32 (5H, m),7.45 (1H, d, J=1 Hz), 8.03 (1H, dd, J=8 Hz, 1 Hz), 8.32 (1H, dd, J=5 Hz,1 Hz)

(9)3-[4-(4-Chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 217°-219° C.

NMR (DMSO-d₆, δ): 0.93 (3H, t, J=7.5 Hz), 1.60-1.82 (2H, m), 2.5 (6H),2.76 (2H, t, J=7.5 Hz), 5.51 (2H, s), 6.90 (1H, d, J=1 Hz), 6.96 (1H,s), 7.15 (2H, d, J=9 Hz), 7.25 (2H, d, J=9 Hz), 7.45 (1H, d, J=1 Hz)

(10)3-[4-[2-Chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.94 (3H, t, J=7.5 Hz), 1.63-1.85 (2H, m), 2.56 (3H,s), 2.81 (2H, t, J=7.5 Hz), 3.69 (3H, s), 5.51 (2H, s), 7.04-7.28 (5H,m), 7.50 (1H, s), 8.17 (1H, d, J=5 Hz)

(11)3-[4-[5-Bromo-1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.89 (3H, t, J=8 Hz), 1.04 (3H, t, J=8 Hz), 1.66 (2H,m), 2.56 (3H, s), 2.81 (2H, t, J=8 Hz), 3.78 (2H, t, J=8 Hz), 5.59 (2H,s), 6.76 (1H, s), 7.08 (1H, d, J=4 Hz), 7.21 (2H, d, J=7 Hz), 7.32 (2H,d, J=7 Hz), 8.18 (1H, d, J=4 Hz)

(12)3-[4-[1-Ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ -CD₃ OD, δ): 0.96 (3H, t, J=7 Hz), 1.20 (3H, t, J=7 Hz), 1.75(2H, m), 2.64 (3H, s), 2.88 (2H, t, J=7 Hz), 3.78 (2H, t, J=7 Hz), 5.58(2H, s), 6.62 (1H, d, J=2 Hz), 6.86 (1H, d, J=2 Hz), 7.11 (1H, d, J=5Hz), 7.17 (2H, d, J=7 Hz), 7.26 (2H, d, J=7 Hz), 8.18 (1H, d, J=5 Hz)

EXAMPLE 28

Sodium hydride (10 mg) (60% in oil) was added to a stirred solution of2-butyl-7-methylimidazo[4,5-b]pyridine (48 mg) in dimethyl sulfoxide(5.0 ml) and the mixture was stirred for 30 minutes at ambienttemperature. To this mixture was added a solution of4-ethoxycarbonyl-1-(4-methanesulfonyloxymethylphenyl)-2-(1-trityl-1H-tetrazol-5-yl)pyrrole(193 mg) in dimethyl sulfoxide (2 ml). The mixture was stirred for 3hours at ambient temperature and poured into brine. The mixture wasextracted with ethyl acetate, dried over magnesium sulfate andevaporated in vacuo. The residue was purified by preparative thin layerchromatography to afford2-butyl-3-[4-[4-ethoxycarbonyl-2-(1-trityl-1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine(123 mg) as a colorless viscous oil.

NMR (CDCl₃, δ): 0.88 (3H, t, J=8 Hz), 1.36 (3H, t, J=8 Hz), 1.24-1.41(2H, m), 1.71 (2H, m), 2.70 (3H, s), 2.74 (2H, t, J=8 Hz), 4.30 (2H, q,J=8 Hz), 5.44 (2H, s), 6.86-7.35 (20H, m), 7.40 (1H, d, J=1.5 Hz), 7.48(1H, d, J=1.5 Hz), 8.20 (1H, d, J=8 Hz)

EXAMPLE 29

A mixture of2-butyl-3-[4-[4-ethoxycarbonyl-2-(1-trityl-1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine(115 mg), conc. hydrochloric acid (0.25 ml) and methanol (20 ml) wasstirred for 2 hours and concentrated under reduced pressure. The residuewas purified by preparative thin layer chromatography to give2-butyl-3-[4-[4-ethoxycarbonyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine[53 mg) as a colorless viscous oil.

NMR (CDCl₃ -CD₃ OD, δ): 0.93 (3H, t, J=8 Hz), 1.36 (3H, t, J=8 Hz), 1.42(2H, m), 1.73 (2H, m), 2.69 (3H, s), 2.90 (2H, t, J=8 Hz), 4.31 (2H, t,J=8 Hz), 5.60 (2H, s), 7.14 (1H, d, J=8 Hz), 7.17-7.31 (6H, m), 8.18(1H, d, J=8 Hz)

EXAMPLE 30

The following compounds were obtained according to a similar manner tothat of Example 3.

(1) Sodium salt of7-methyl-2-propyl-3-[4-[2-(1H-tetrazol-5-yl)-4-trifluoromethyl-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.56 (3H, t, J=7 Hz), 1.39 (2H, dt, J=7.7 Hz), 2.35 (3H,s), 2.56 (2H, t, J=7 Hz), 5.21 (2H, s), 6.57 (2H, d, J=8 Hz), 6.67-6.83(5H), 7.79 (1H, d, J=8 Hz)

(2) Sodium salt of5,7-dimethyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.69 (3H, t, J=7 Hz), 1.37 (2H, m), 1.80 (3H, s), 2.37(6H, s), 2.67 (2H, t, J=7 Hz), 5.34 (2H, s), 6.07 (1H, d, J=4 Hz), 6.60(1H, d, J=4 Hz), 6.71 (1H, s), 6.84 (2H, d, J=8 Hz), 6.96 (2H, d, J=8Hz)

(3) Sodium salt of3-[4-[2,3-dimethyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 123°-129.5° C.

NMR (D₂ O, δ): 0.63 (3H, t, J=7.5 Hz), 1.22-1.52 (2H, m), 1.45 (3H, s),1.82 (3H, s), 2.35 (3H, s), 2.65 (2H, t, J=7.5 Hz), 5.30 (2H, s), 6.48(1H, s), 6.65 (2H, d, J=9.0 Hz), 6.77 (1H, d, J=5.0 Hz), 6.88 (2H, d,J=9.0 Hz), 7.87 (1H, d, J=5.0 Hz)

(4) Sodium salt of3-[4-[2-chloro-3-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.48 (3H, t, J=7.5 Hz), 1.12-1.39 (2H, m), 1.60 (3H, s),2.26 (3H, s), 2.51 (2H, t, J=7.5 Hz), 5.21 (2H, s), 6.46 (1H, s),6.58-6.71 (3H, m), 6.83 (2H, d, J=9.0 Hz), 7.81 (1H, d, J=5.0 Hz)

(5) Sodium salt of3-[4-(2-bromo-3-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.50 (3H, t, J=7.5 Hz), 1.10-1.49 (2H, m), 1.62 (3H, s),2.26 (3H, s), 2.50 (2H, t, J=7.5 Hz), 5.22 (2H, s), 6.50 (1H, s),6.57-6.72 (3H, m), 6.83 (2H, d, J=9 Hz), 7.83 (1H, d, J=5 Hz)

(6) Sodium salt of2-ethyl-5,7-dimethyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 177°-181° C.

NMR (D₂ O, δ): 1.00 (3H, t, J=7 Hz), 1.63 (3H, s), 2.26 (3H x 2, s),2.65 (2H, q, J=7 Hz), 5.76 (2H, s), 5.96 (1H, d, J=3 Hz), 6.46 (1H, s),6.59 (1H, d, J=3 Hz), 6.72 (2H, d, J=8 Hz), 6.90 (2H, d, J=8 Hz)

(7) Sodium salt of3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-ethyl-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 1.11 (3H, t, J=7.5 Hz), 2.43 (3H, s), 2.70 (2H, q, J=7.5Hz), 5.30 (2H, s), 6.44 (1H, d, J=2 Hz), 6.51-6.63 (3H, m), 6.78 (2H, d,J=9 Hz), 6.89 (1H, d, J=5 Hz), 7.88 (1H, d, J=5 Hz)

(8) Sodium salt of3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.80 (3H, t, J=7.5 Hz), 1.45-1.71 (2H, m), 2.70 (2H, t,J=7.5 Hz), 5.40 (2H, s), 6.56-6.76 (4H, m), 6.86 (2H, d, J=9 Hz), 7.22(1H, dd, J=8 Hz, 5 Hz), 7.95 (1H, dd, J=8 Hz, 1 Hz), 8.14 (1H, dd, J=5Hz, 1 Hz)

(9) Sodium salt of3-[4-[4-Chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.73 (3H, t, J=7.5 Hz), 1.34-1.59 (2H, m), 2.33 (3H, s),2.37 (3H, s), 2.64 (2H, t, J=7.5 Hz), 5.30 (2H, s), 6.43 (1H, d, J=1Hz), 6.50-6.72 (4H, m), 6.80 (2H, d, J=9 Hz)

(10) Sodium salt of2-butyl-3-[4-[4-ethoxycarbonyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.68 (3H, t, J=8 Hz), 1.17 (2H, t, J=8 Hz), 1.15 (2H, m),1.43 (2H, m), 2.44 (3H, s), 2.64 (2H, t, J=8 Hz), 4.11 (2H, q, J=8 Hz),5.31 (2H, s), 6.71 (2H, d, J=8 Hz), 6.88 (2H, d, J=8 Hz), 6.90 (1H, d,J=5 Hz), 6.96 (1H, d, J=1.5 Hz), 6.98 (1H, d, J=1.5 Hz), 7.90 (1H, d,J=5 Hz)

(11) Sodium salt of3-[4-[2-chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.70 (3H, t, J=7.5 Hz), 1.33-1.58 (2H, m), 2.37 (3H, s),2.62 (2H, t, J=7.5 Hz), 3.33 (3H, s), 6.74-6.93 (5H, m), 7.07 (1H, s),7.93 (1H, d, J=5 Hz)

(12) Sodium salt of3-[4-[5-bromo-1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.45 (3H, t, J=7 Hz), 0.58 (3H, t, J=7 Hz), 1.35 (2H, m),2.30 (3H, s), 2.63 (2H, t, J=7 Hz), 3.20 (2H, m), 5.30 (2H, s), 6.56(1H, s), 6.71 (1H, d, J=4 Hz), 6.79 (2H, d, J=7 Hz), 6.95 (2H, d, J=7Hz), 7.83 (1H, d, J=4 Hz)

(13) Sodium salt of3-[4-[1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.65 (3H, t, J=7 Hz), 0.73 (3H, t, J=7 Hz), 1.35 (2H, m),2.32 (3H, s), 2.65 (2H, t, J=7 Hz), 3.34 (2H, q, J=7 Hz), 5.28 (2H, s),6.57 (1H, d, J=1 Hz), 6.75 (1H, d, J=1 Hz), 6.76 (1H, d, J=5 Hz), 6.82(2H, d, J=8 Hz), 6.89 (2H, d, J=8 Hz), 7.83 (1H, d, J=5 Hz)

EXAMPLE 31

7-Methyl-3-[4-[5-methyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine(13.1 g) was dissolved in hot ethanol (70 ml) and conc. hydrochloricacid (3.2 ml) was added therein. The mixture was stirred for 1 hour atambient temperature and the precipitate was collected by vacuumfiltration to give a white powder (11.7 g). This was recrystallized frommethanol - 1N hydrochloric acid to afford7-methyl-3-[4-[5-methyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridinehydrochloride (9.13 g) as colorless fine crystals.

mp: 241°-243° C.

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=7 Hz), 1.69 (2H, m), 2.00 (3H, s), 2.70(3H, s), 3.18 (2H, t, J=7 Hz), 5.82 (2H, s), 6.20 (1H, d, J=4 Hz), 6.88(1H, d, J=4 Hz), 7.27 (2H, d, J=8 Hz), 7.40 (2H, d, J=8 Hz), 7.46 (1H,d, J=4 Hz), 8.50 (1H, d, J=4 Hz)

EXAMPLE 32

A mixture of3-[4-(2-cyano-3-furyl)benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine(540 mg) and trimethyltin azide (1.095 g) in xylene (10 ml) was stirredat 125° C. for 24 hours. The mixture was concentrated in vacuo. Theresidue was dissolved in methanol (15 ml) and the methanolic solutionwas treated with 8.9N methanolic hydrogen chloride (1 ml) for one hourat ambient temperature. The mixture was adjusted to pH 5 with aqueous 1Nsodium hydroxide solution and concentrated in vacuo. The residue waspurified by flash column chromatography on silica gel (elution bydichloromethane/methanol=15/1-8/1) to yield7-methyl-2-propyl-3-[4-[2-(1H-tetrazol-5-yl)-3-furyl]benzyl]-3H-imidazo[4,5-b]pyridine(525 mg) as an amorphous solid.

NMR (DMSO-d₆, δ): 0.95 (3H, t, J=7.5 Hz), 1.64-1.87 (2H, m), 2.58 (3H,s), 2.83 (2H, t, J=7.5 Hz), 5.55 (2H, s), 7.00 (1H, d, J=1 Hz), 7.05(1H, d, J=5 Hz), 7.20 (2H, d, J=9 Hz), 7.75 (2H, d, J=9 Hz), 8.02 (1H,d, J=1 Hz), 8.17 (1H, d, J=5 Hz)

EXAMPLE 33

7-Methyl-2-propyl-3-[4-[2-(1H-tetrazol-5-yl)-3-furyl]benzyl]-3H-imidazo[4,5-b]pyridine(520 mg) was dissolved in aqueous 1N sodium hydroxide solution (1.3 ml).The solution was filtered and the filtrate was lyophilized to givesodium salt of7-methyl-2-propyl-3-[4-[2-(1H-tetrazol-5-yl)-3-furyl]benzyl]-3H-imidazo-4,5-b]pyridine(505 mg).

NMR (D₂ O, δ): 0.75 (3H, t, J=7.5 Hz), 1.36-1.60 (2H, m), 2.40 (3H, s),2.60 (2H, t, J=7.5 Hz), 5.21 (2H, s), 6.36 (1H, d, J=1 Hz), 6.74 (2H, d,J=9 Hz), 6.87 (1H, d, J=5 Hz), 6.98 (2H, d, J=9 Hz), 7.54 (1H, d, J=1Hz), 7.90 (1H, d, J=5 Hz)

EXAMPLE 34

The following compounds were obtained according to a similar manner tothat of Example 1.

(1)2-Butyl-3-[4-[2-(1H-tetrazol-5-yl)-3-benzo[b]furyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 244°-248° C.

NMR (DMSO-d₆, δ): 0.88 (3H, t, J=7.5 Hz), 1.28-1.49 (2H, m), 1.63-1.82(2H, m), 2.91 (2H, t, J=7.5 Hz), 5.59 (2H, s), 7.18-7.40 (5H, m), 7.58(1H, d, J=7.5 Hz), 7.62-7.75 (1H, m), 7.69 (2H, d, J=8.0 Hz), 8.02 (1H,dd, J=9.0 Hz and 0.5 Hz), 8.33 (1H, dd, J=5.0 Hz, 0.5 Hz)

(2)2-Butyl-3-[4-[3-(1H-tetrazol-5-yl)-2-benzo[b]thienyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 75°-77° C.

NMR (DMSO-d₆, δ): 0.87 (3H, t, J=7 Hz), 1.36 (2H, m), 1.71 (2H, m), 2.86(2H, t, J=7 Hz), 5.54 (2H, s), 7.14 (2H, d, J=8 Hz), 7.20-7.50 (5H),7.72 (1H, m), 7.98-8.10 (2H), 8.30 (1H, d, J=5 Hz)

(3)2-Butyl-3-[4-[1-bromo-3-(1H-tetrazol-5-yl)-2-indolizinyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ -CD₃ OD, δ): 0.93 (3H, t, J=7 Hz), 1.43 (2H, m), 1.79 (2H,m), 2.93 (2H, t, J=7 Hz), 5.64 (2H, s), 6.86 (1H, dd, J=7 Hz and 1 Hz),7.11 (1H, dd, J=7 Hz and 8 Hz), 7.21 (2H, d, J=8 Hz), 7.32 (1H, m), 7.35(2H, d, J=8 Hz), 7.57 (1H, d, J=8 Hz), 8.05 (1H, dd, J=8 Hz and 1 Hz),8.36 (1H, dd, J=7 Hz and 1 Hz), 9.10 (1H, d, J=7 Hz)

(4) 2-Butyl-3-[4-[1-bromo-3-(1H-tetrazol-5-yl)-2-indolizinyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃ -CD₃ OD, δ): 0.92 (3H, t, J=7 Hz), 1.44 (2H, m), 1.86 (2H,m), 3.02 (2H, t, J=7 Hz), 5.62 (2H, s), 6.93 (1H, dd, J=7 Hz), 7.17 (1H,ddd, J=1 Hz, 7 Hz and 8 Hz), 7.24-7.45 (5H, m), 8.15 (2H, dt, J=1 Hz and7 Hz), 8.43 (1H, dd, J=1 Hz and 5 Hz), 8.52 (1H, d, J=8 Hz)

(5)3-[4-[2-Chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-5,7-dimethyl-2-ethyl-3H-imidazo4,5-b]pyridine

mp: 224°-226° C.

NMR (DMSO-d₆, δ): 1.26 (3H, t, J=7.5 Hz), 2.52 (6H, s), 2.81 (2H, q,J=7.5 Hz), 3.69 (3H, s), 5.48 (2H, s), 6.96 (1H, s), 7.10 (2H, d, J=9Hz), 7.21 (2H, d, J=9 Hz), 7.51 (1H, s)

(6)3-[4-[1,2-Dimethyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 124°-130° C.

NMR (DMSO-d₆, δ): 0.92 (3H, t, J=7.5 Hz), 1.61-1.83 (2H, m), 2.12 (3H,s), 2.56 (3H, s), 2.83 (2H, t, J=7.5 Hz), 3.62 (3H, s), 5.50 (2H, s),7.03-7.18 (5H, m), 7.30 (1H, s), 8.17 (1H, d, J=5 Hz)

(7)7-Methyl-2-propyl-3-[4-[1-propyl-3-[1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.63 (3H, t, J=8 Hz), 0.88 (3H, t, J=8 Hz), 1.45 (2H,m), 1.66 (2H, m), 2.56 (3H, s), 2.83 (2H, t, J=8 Hz), 3.72 (2H, t, J=8Hz), 5.58 (2H, s), 6.58 (1H, d, J=4 Hz), 7.07 (1H, d, J=4 Hz), 7.09 (1H,d, J=5 Hz), 7.10 (2H, d, J=9 Hz), 7.20 (2H, d, J=9 Hz), 8.17 (1H, d, J=5Hz)

(8)5,7-Dimethyl-2-ethyl-3-[4-[1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 252°-254° C.

NMR (DMSO-d₆, δ): 1.11 (3H, t, J=8 Hz), 1.23 (3H, t, J=8 Hz), 2.44 (3H,s), 2.47 (3H, s), 2.81 (2H, q, J=8 Hz), 3.77 (2H, q, J=8 Hz), 5.51 (2H,s), 6.58 (1H, d, J=3 Hz), 6.95 (1H, s), 7.10 (1H, d, J=3 Hz), 7.19 (2H,d, J=9 Hz), 7.31 (2H, d, J=9 Hz)

(9)3-[4-[1-Isopropyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=8 Hz), 1.28 (6H, d, J=8 Hz), 1.70 (2H,m), 2.56 (3H, s), 2.82 (2H, t, J=8 Hz), 4.07 (1H, m), 5.57 (2H, s), 6.61(1H, d, J=3 Hz), 7.09 (1H, d, J=5 Hz), 7.19 (1H, d, J=3 Hz), 7.22 (2H,d, J=9 Hz), 7.29 (2H, d, J=9 Hz), 8.17 (1H, d, J=5 Hz)

(10) 3-[4-[2-Chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 147°-150° C.

NMR (DMSO-d₆, δ): 0.91 (3H, t, J=7.5 Hz), 1.60-1.81 (2H, m), 2.51 (6H,s), 2.77 (2H, t, J=7.5 Hz), 3.70 (3H, s), 5.48 (2H, s), 6.96 (1H, s),7.10 (2H, d, J=9 Hz), 7.21 (2H, d, J=9 Hz), 7.51 (1H, s)

(11)5,7-Dimethyl-3-[4-[1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 209°-212° C.

NMR (DMSO-d₆, δ): 0.86 (3H, t, J=8 Hz), 1.11 (3H, t, J=8 Hz), 1.68 (2H,m), 2.50 (3H, s), 2.53 (3H, s), 2.75 (2H, t, J=8 Hz), 3.78 (2H, q, J=8Hz), 5.55 (2H, s), 6.60 (1H, d, J=3 Hz), 6.98 (1H, s), 7.10 (1H, d, J=3Hz), 7.17 (2H, d, J=9 Hz), 7.31 (2H, d, J=9 Hz)

EXAMPLE 35

The following compounds were obtained according to a similar manner tothat of Example 28.

(1)2-Butyl-3-[4-[5-chloro-2-(1-trityl-1H-tetrazol-5-yl)-3-thienyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.88 (3H, t, J=6 Hz), 1.38 (2H, m), 1.79 (2H, m), 2.85(2H, t, J=6 Hz), 5.52 (2H, s), 6.90-7.40 (21H), 8.14 (1H, d, J=8 Hz),8.43 (1H, dd, J=5 Hz and 1 Hz)

(2)2-Butyl-3-[4-[3-(1-trityl-1H-tetrazol-5-yl)-2-imidazo[1,2-a]pyridyl]benzyl]-3H-imdazo[4,5-b]pyridine

NMR (CDCl₃, δ): 0.88 (1.5H, t, J=7 Hz), 0.97 (1.5H, t, J=7 Hz),1.18-1.60 (2H, m), 1.68-2.03 (2H, m), 2.76 (1H, t, J=7 Hz), 3.05 (1H, t,J=7 Hz), 5.52 (2H, s), 6.91 (1H, dd, J=1 Hz and 7 Hz), 7.06-7.63 (18H,m), 7.73 (1H, t, J=7 Hz), 7.83 (2H, d, J=8 Hz), 8.07 (2H, d, J=8 Hz),8.88 (1H, dd, J=1 Hz and 8 Hz), 9.09 (1H, d, J=8 Hz)

EXAMPLE 36

The following compound was obtained according to a similar manner tothat of Example 29.

2-Butyl-3-[4-[3-(1H-tetrazol-5-yl)-2-imidazo[1,2-a]pyridyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (CD₃ OD, δ): 0.80 (3H, t, J=7 Hz), 1.30 (2H, m), 1.66 (2H, m), 2.74(2H, t, J=7 Hz), 5.45 (2H, s), 6.86 (1H, t, J=7 Hz), 7.04 (2H, d, J=8Hz), 7.18 (1H, d, J=5 Hz), 7.23 (1H, d, J=5 Hz), 7.31 (1H, br t, J=8Hz), 7.62 (2H, d, J=8 Hz), 7.93 (1H, dd, J=1 Hz and 8 Hz), 8.24 (1H, dd,J=1 Hz and 7 Hz), 8.40 (1H, d, J=8 Hz)

EXAMPLE 37

2-Butyl-3-[4-[5-chloro-2-(1-trityl-1H-tetrazol-5-yl)-3-thienyl]benzyl]-3H-imidazo[4,5-b]pyridine(1.02 g) was dissolved in 1,4-dioxane (10 ml) and treated with 1Nhydrochloric acid at ambient temperature for 10 hours. The reactionmixture was neutralized with 1N aqueous sodium hydroxide andconcentrated in vacuo. The residue was extracted withdichloromethane-methanol (4:1) and the extract was evaporated in vacuo.The residue was purified by silica gel column chromatography to afford2-butyl-3-[4-[5-chloro-2-(1H-tetrazol-5-yl)-3-thienyl]benzyl]-3H-imidazo[4,5-b]pyridine(640 mg).

NMR (DMSO-d₆, δ): 0.87 (3H, t, J=6 Hz), 1.37 (2H, m), 1.72 (2H, m), 2.86(2H, t, J=6 Hz), 5.54 (2H, s), 7.16 (2H, d, J=8 Hz), 7.27 (1H, dd, J=8Hz and 5 Hz), 7.40 (2H, d, J=8 Hz), 8.02 (1H, dd, J=8 Hz and 1 Hz), 8.30(1H, dd, J=5 Hz and 1 Hz)

EXAMPLE 38

The following compounds were obtained according to a similar manner tothat of Example 3.

(1) Sodium salt of3-[4-[2-chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine

mp: 107°-112° C.

NMR (D₂ O, δ): 1.00 (3H, t, J=7.5 Hz), 2.19 (3H, s), 2.23 (3H, s), 2.55(2H, q, J=7.5 Hz), 3.20 (3H, s), 5.19 (2H, s), 6.48 (1H, s), 6.66-6.84(4H, m), 7.00 (1H, s)

(2) Sodium salt of3-[4-[1,2-dimethyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.78 (3H, t, J=7.5 Hz), 1.40-1.62 (2H, m), 1.78 (3H, s),2.46 (3H, s), 2.71 (2H, t, J=7.5 Hz), 3.45 (3H, s), 5.35 (2H, s), 6.73(2H, d, J=9 Hz), 6.85 (2H, d, J=9 Hz), 6.97 (1H, d, J=5 Hz), 7.07 (1H,s), 7.98 (1H, d, J=5 Hz)

(3) Sodium salt of7-methyl-2-propyl-3-[4-[1-propyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.28 (3H, t, J=8 Hz), 0.62 (3H, t, J=8 Hz), 1.07 (2H, m),1.34 (2H, m), 2.37 (3H, s), 2.65 (2H, t, J=8 Hz), 3.28 (2H, t, J=8 Hz),5.33 (2H, s), 6.53 (1H, d, J=3 Hz), 6.68 (1H, d, J=3 Hz), 6.78 (1H, d,J=5 Hz), 6.89 (2H, d, J=9 Hz), 6.94 (2H, d, J=9 Hz), 7.90 (1H, d, J=5Hz)

(4) Sodium salt of5,7-dimethyl-2-ethyl-3-[4-[1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.78 (3H, t, J=8 Hz), 1.05 (3H, t, J=8 Hz), 2.29 (6H, s),2.67 (2H, q, J=8 Hz), 3.40 (2H, q, J=8 Hz), 5.79 (2H, s), 6.55 (1H, d,J=3 Hz), 6.56 (1H, s), 6.78 (1H, d, J=3 Hz), 6.86 (2H, d, J=9 Hz), 6.91(2H, d, J=9 Hz)

(5) Sodium salt of3-[4-[1-isopropyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.68 (3H, t, J=8 Hz), 0.92 (6H, d, J=7 Hz), 1.40 (2H, m),2.39 (3H, s), 2.69 (2H, t, J=7 Hz), 3.82 (1H, m), 5.34 (2H, s), 6.56(1H, d, J=3 Hz), 6.84 (1H, d, J=5 Hz), 6.85 (1H, d, J=3 Hz), 6.91 (2H,d, J=9 Hz), 6.98 (2H, d, J=9 Hz), 7.90 (1H, d, J=5 Hz)

(6) Sodium salt of5,7-dimethyl-3-[4-[1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.64 (3H, t, J=8 Hz), 0.80 (3H, t, J=8 Hz), 1.35 (2H, m),2.27 (3H, s), 2.31 (3H, s), 2.63 (2H, t, J=8 Hz), 3.45 (2H, q, J=8 Hz),5.82 (2H, s), 6.56 (1H, d, J=3 Hz), 6.61 (1H, s), 6.79 (1H, d, J=3 Hz),6.89 (2H, d, J=9 Hz), 6.94 (2H, d, J=9 Hz)

EXAMPLE 39

A mixture of2-butyl-3-[4-[5-chloro-2-(1H-tetrazol-5-yl)-3-thienyl]benzyl]-3H-imidazo[4,5-b]pyridine(330 mg), 10% palladium on carbon (103 mg), potassium hydroxide (261 mg)and methanol (15 ml) was stirred under hydrogen atmosphere (1 atm) atambient temperature for 3 hours. The reaction mixture was filteredthrough cellulose powder and the filtrate was evaporated in vacuo. Theresidue was dissolved in water and neutralized with 1N hydrochloricacid. The precipitate was collected by vacuum filtration to afford awhite powder of2-butyl-3-[4-[2-(1H-tetrazol-5-yl)-3-thienyl]benzyl]-3H-imidazo[4,5-b]pyridine(279 mg).

NMR (DMSO-d₆, δ): 0.88 (3H, t, J=6 Hz), 1.37 (2H, m), 1.71 (2H, m), 2.88(2H, t, J=6 Hz), 5.56 (2H, s), 7.19 (2H, d, J=8 Hz), 7.24-7.40 (4H),7.94 (1H, d, J=5 Hz), 8.03 (1H, dd, J=8 Hz and 1 Hz), 8.32 (1H, dd, J=5Hz and 1 Hz)

EXAMPLE 40

The following compounds were obtained according to a similar manner tothat of Example 39.

(1)2-Butyl-3-[4-[3-(1H-tetrazol-5-yl)-2-indolizinyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 152°-154° C.

NMR (CDCl₃ -CD₃ OD, Δ): 0.96 (3H, t, J=7 Hz), 1.45 (2H, m), 1.80 (2H,m), 2.92 (2H, t, J=7 Hz), 5.60 (2H, s), 6.66 (1H, s), 6.78 (1H, dt, J=1Hz and 7 Hz), 6.98 (1H, ddd, J=1 Hz, 7 Hz and 8 Hz), 7.18 (2H, d, J=7Hz), 7.34 (2H, d, J=7 Hz), 7.35 (1H, m), 8.05 (1H, dd, J=8 Hz and 1 Hz),8.35 (1H, dd, J=1 Hz and 7 Hz), 8.93 (1H, d, J=8 Hz)

(2) 2-Butyl-3-[4-[1-(1H-tetrazol-5-yl)-2-indolizinyl]benzyl]-3H-imidazo[4,5-b]pyridine

mp: 183°-185° C.

NMR (CDCl₃ -CD₃ OD, δ): 0.93 (3H, t, J=7 Hz), 1.43 (2H, m), 1.79 (2H,m), 2.97 (2H, t, J=7 Hz), 5.63 (2H, s), 6.74 (1H, t, J=7 Hz), 7.03 (1H,dd, J=7 Hz and 8 Hz), 7.18 (2H, d, J=7 Hz), 7.29 (1H, s), 7.40 (1H, m),7.50 (2H, d, J=7 Hz), 7.91 (1H, d, J=8 Hz), 8.10 (2H, d, J=7 Hz), 8.43(1H, d, J=5 Hz)

EXAMPLE 41

The following compounds were obtained according to a similar manner tothat of Example 1.

(1)3-[4-[5-Chloro-1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 213°-214° C.

NMR (CDCl₃ -CD₃ OD, δ): 1.01 (3H, t, J=7 Hz), 1.18 (3H, t, J=7 Hz), 1.80(2H, m), 2.71 (3H, s), 2.95 (2H, t, J=7 Hz), 3.89 (2H, q, J=7 Hz), 5.63(2H, s), 6.60 (1H, s), 7.15 (1H, d, J=5 Hz), 7.22 (2H, d, J=9 Hz), 7.30(2H, d, J=9 Hz), 7.49 (1H, s), 8.23 (1H, d, J=5 Hz)

(2)3-[4-[5-Chloro-1-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 190°-191° C.

NMR (DMSO-d₆, δ): 0.93 (3H, t, J=7 Hz), 1.72 (2H, m), 2.57 (3H, s), 2.84(2H, d, J=7 Hz), 3.37 (3H, s), 5.58 (2H, s), 6.67 (1H, s), 7.10 (1H, d,J=5 Hz), 7.22 (2H, d, J=9 Hz), 7.37 (2H, d, J=9 Hz), 8.18 (1H, d, J=5Hz)

(3)3-[4-[5-Chloro-1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 254°-261° C. (dec.)

NMR (CDCl₃ -CD₃ OD, δ): 1.17 (3H, t, J=7.5 Hz), 1.34 (3H, t, J=7.5 Hz),2.61 (3H, s), 2.63 (3H, s), 2.89 (2H, q, J=7.5 Hz), 3.88 (2H, q, J=7.5Hz), 5.58 (2H, s), 6.60 (2H, s), 7.00 (1H, s), 7.20 (2H, d, J=9 Hz),7.30 (2H, d, J=9 Hz)

(4)3-[4-[5-Chloro-1-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 244°-245° C. (dec.)

NMR (DMSO-d₆, δ): 1.25 (3H, t, J=7 Hz), 2.51 (6H, s), 2.82 (2H, q, J=7Hz), 5.53 (2H, s), 6.68 (1H, s), 6.97 (1H, s), 7.20 (2H, d, J=9 Hz),7.37 (2H, d, J=9 Hz)

(5)3-[4-[5-Chloro-1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 211°-213° C.

NMR (CDCl₃ -CD₃ OD, δ): 0.96 (3H, t, J=7 Hz), 1.18 (3H, t, J=7 Hz), 1.75(2H, m), 2.60 (3H, s), 2.65 (3H, s), 2.83 (2H, t, J=7 Hz), 3.39 (2H, q,J=7 Hz), 5.59 (2H, s), 6.60 (1H, s), 6.99 (1H, s), 7.20 (2H, d, J=9 Hz),7.30 (2H, d, J=9 Hz)

(6)3-[4-[5-Chloro-1-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 191°-193° C.

NMR (CDCl₃ -CD₃ OD, δ): 0.99 (3H, t, J=7 Hz), 1.77 (2H, m), 2.60 (3H,s), 2.62 (3H, s), 2.84 (2H, t, J=7 Hz), 3.46 (3H, s), 5.57 (2H, s), 6.60(1H, s), 6.99 (1H, s), 7.19 (2H, d, J=9 Hz), 7.29 (2H, d, J=9 Hz)

(7)3-[4-[1,5-Dimethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 238°-241° C.

NMR (DMSO-d₆, δ): 1.26 (3H, t, J=7.5 Hz), 2.27 (3H, s), 2.50 (6H, s),2.83 (2H, q, J=7.5 Hz), 3.31 (3H, s), 5.52 (2H, s), 6.36 (1H, s), 6.97(1H, s), 7.18 (2H, d, J=9.0 Hz), 7.31 (2H, d, J=9.0 Hz)

(8)3-[4-[1-Ethyl-5-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 261.5°-262.5° C.

NMR (DMSO-d₆, δ): 1.02 (3H, t, J=7.0 Hz), 1.22 (3H, t, J=7.5 Hz), 2.29(3H, s), 2.51 (6H, s), 2.82 (2H, q, J=7.5 Hz), 3.73 (2H, q, J=7.0 Hz),5.53 (2H, s), 6.34 (1H, s), 6.97 (1H, s), 7.19 (2H, d, J=9.0 Hz), 7.30(2H, d, J=9.0 Hz)

(9)3-[4-[1,5-Dimethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 202°-204.5° C.

NMR (DMSO-d₆, δ): 0.93 (3H, t, J=7.5 Hz), 1.62-1.83 (2H, m), 2.27 (3H,s), 2.57 (3H, s), 2.86 (2H, t, J=7.5 Hz), 3.32 (3H, s), 5.58 (2H, s),6.34 (1H, s), 7.09 (1H, d, J=5.0 Hz), 7.21 (2H, d, J=9.0 Hz), 7.32 (2H,d, J=9.0 Hz), 8.17 (1H, d, J=5.0 Hz)

(10)3-[4-[1-Ethyl-5-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 176°-178° C.

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=7.5 Hz), 1.00 (3H, t, J=7.0 Hz),1.58-1.80 (2H, m), 2.29 (3H, s), 2.58 (3H, s), 2.82 (2H, t, J=7.5 Hz),3.71 (2H, q, J=7.0 Hz), 5.58 (2H, s), 6.34 (1H, s), 7.10 (1H, d, J=5.0Hz), 7.21 (2H, d, J=9.0 Hz), 7.30 (2H, d, J=9.0 Hz), 8.20 (1H, d, J=5.0Hz)

(11)3-[4-[1,5-Dimethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]-benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 148°-153° C.

NMR (DMSO-d₆, δ): 0.91 (3H, t, J=7.5 Hz), 1.59-1.82 (2H, m), 2.27 (3H,s), 2.80 (2H, t, J=7.5 Hz), 3.32 (3H, s), 5.53 (2H, s), 6.35 (1H, s),6.97 (1H, s), 7.17 (2H, d, J=9 Hz), 7.31 (2H, d, J=9 Hz)

(12)3-[4-1-Ethyl-5-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 208°-209° C.

NMR (DMSO-d₆, δ): 0.88 (3H, t, J=7 Hz), 1.00 (3H, t, J=7 Hz), 1.66 (2H,m), 2.30 (3H, s), 2.50 (6H, s), 2.77 (2H, q, J=7 Hz), 3.73 (2H, q, J=7Hz), 5.54 (2H, s), 6.34 (1H, s), 6.97 (1H, s), 7.18 (2H, d, J=9 Hz),7.30 (2H, d, J=9 Hz)

(13)3-[4-[2-Bromo-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 229°-231° C.

NMR (DMSO-d₆, δ): 1.25 (3H, t, J=7.5 Hz), 2.81 (2H, q, J=7.5 Hz), 3.71(3H, s), 5.48 (2H, s), 6.95 (1H, s), 7.10 (2H, d, J=9 Hz), 7.20 (2H, d,J=9 Hz), 7.63 (1H, s)

(14)3-[4-[2-Bromo-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imdazo[4,5-b]pyridine

mp: 151°-153° C.

NMR (DMSO-d₆, δ): 0.91 (3H, t, J=7.5 Hz), 1.59-1.82 (2H, m), 2.76 (2H,t, J=7.5 Hz), 3.71 (3H, s), 5.48 (2H, s), 6.95 (1H, s), 7.10 (2H, d, J=9Hz), 7.20 (2H, d, J=9 Hz), 7.63 (1H, s)

EXAMPLE 42

The following compounds were obtained according to a similar manner tothat of Example 3.

(1) Sodium salt of3-[4-[5-chloro-1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.57 (3H, t, J=7 Hz), 0.64 (3H, t, J=7 Hz), 1.38 (2H, m),2.35 (3H, s), 2.68 (2H, t, J=7 Hz), 3.29 (2H, br q, J=7 Hz), 5.36 (2H,s), 6.44 (1H, s), 6.80 (1H, d, J=5 Hz), 6.83 (2H, d, J=9 Hz), 6.95 (2H,d, J=9 Hz), 7.88 (1H, d, J=5 Hz)

(2) Sodium salt of3-[4-[5-chloro-1-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.77 (3H, t, J=7 Hz), 1.50 (2H, s), 2.40 (3H, s), 2.71(2H, t, J=7 Hz), 2.89 (3H, s), 5 35 (2H, s), 6.47 (1H, s), 6.73 (2H, d,J=5 Hz), 6.82-6.92 (3H), 7.91 (1H, d, J=5 Hz)

(3) Sodium salt of3-[4-[5-chloro-1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.53 (3H, t, J=7 Hz), 1.02 (3H, t, J=7 Hz), 2.24 (6H, s),2.66 (2H, q, J=7 Hz), 3.24 (2H, br q, J=7 Hz), 5.80 (2H, br s), 6.43(1H, s), 6.50 (1H, s), 6.80 (2H, d, J=9 Hz), 6.93 (2H, d, J=9 Hz)

(4) Sodium salt of3-[4-[5-chloro-1-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 1.11 (3H, t, J=7 Hz), 2.29 (6H, s), 2.70 (2H, q, J=7 Hz),2.82 (3H, s), 5.30 (2H, s), 6.43 (1H, s), 6.64 (1H, s), 6.72 (2H, d, J=9Hz), 6.88 (2H, d, J=9 Hz)

(5) Sodium salt of3-[4-[5-chloro-1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 172°-176° C.

NMR (DMSO-d₆, δ): 0.89 (3H, t, J=7 Hz), 1.02 (3H, t, J=7 Hz), 1.68 (2H,m), 2.49 (3H, s), 2.51 (3H, s), 2.76 (2H, t, J=7.5 Hz), 3.75 (2H, q, J=7Hz), 5.50 (2H, s), 6.36 (1H, s), 6.95 (1H, s), 7.10 (2H, d, J=9 Hz),7.35 (2H, d, J=9 Hz)

(6) Sodium salt of3-[4-[5-chloro-1-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.68 (3H, t, J=7.5 Hz), 1.40 (2H, m), 2.26 (6H, s), 2.60(2H, t, J=8 Hz), 2.71 (3H, s), 5.78 (2H, s), 6.44 (1H, s), 6.58 (1H, s),6.73 (2H, d, J=9 Hz), 6.87 (2H, d, J=9 Hz)

(7) Sodium salt of3-[4-[1,5-dimethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 1.08 (3H, t, J=7.5 Hz), 2.07 (3H, s), 2.30 (6H, s), 2.68(2H, q, J=7.5 Hz), 2.85 (3H, s), 5.28 (2H, s), 6.28 (1H, s), 6.65 (1H,s), 6.80 (2H, d, J=9.0 Hz), 6.88 (2H, d, J=9.0 Hz)

(8) Sodium salt of 3-[4-[1-ethyl-5-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 138.5°-148° C.

NMR (DMSO-d₆, δ): 0.97 (3H, t, J=7.5 Hz), 1.23 (3H, t, J=7.5 Hz), 2.24(3H, s), 2.80 (2H, q, J=7.5 Hz), 3.69 (2H, q, J=7.5 Hz), 5.48 (2H, s),6.10 (1H, s), 6.95 (1H, s), 7.07 (2H, d, J=9 Hz), 7.31 (2H, d, J=9 Hz)

(9) Sodium salt of3-[4-[1,5-dimethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.75 (3H, t, J=7.5 Hz), 1.48 (2H, m), 2.11 (3H, s), 2.42(3H, s), 2.69 (2H, t, J=7.5 Hz), 2.90 (3H, s), 5.33 (2H, s), 6.30 (1H,s), 6.80 (2H, d, J=9.0 Hz), 6.87 (2H, d, J=9.0 Hz), 6.89 (1H, d, J=5.0Hz), 7.90 (1H, d, J=5.0 Hz)

(10) Sodium salt of3-[4-[1-ethyl-5-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.60 (3H, t, J=7.5 Hz), 0.64 (3H, t, J=7.0 Hz), 1.26-1.49(2H, m), 2.10 (3H, s), 2.38 (3H, s), 2.68 (2H, t, J=7.5 Hz), 3.28 (2H,q, J=7.0 Hz), 5.32 (2H, s), 6.30 (1H, s), 6.81 (1H, d, J=5.0 Hz), 6.85(2H, d, J=9.0 Hz), 6.94 (2H, d, J=9.0 Hz), 7.90 (1H, d, J=5.0 Hz)

(11) Sodium salt of3-[4-[1,5-dimethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 112°-113° C.

NMR (DMSO-d₆, δ): 0.93 (3H, t, J=7.5 Hz), 1.60-1.84 (2H, m), 2.23 (3H,s), 2.79 (2H, t, J=7.5 Hz), 3.28 (3H, s), 5.46 (2H, s), 6.11 (1H, s),6.95 (1H, s), 7.06 (2H, d, J=9 Hz), 7.48 (2H, d, J=9 Hz)

(12) Sodium salt of3-[4-[1-ethyl-5-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 165°-173° C.

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=7 Hz), 0.98 (3H, t, J=7 Hz), 1.68 (2H,m), 2.25 (3H, s), 2.52 (6H, s), 2.77 (2H, t, J=7 Hz), 3.69 (2H, q, J=7Hz), 5.49 (2H, s), 6.11 (1H, s), 6.95 (1H, s), 7.07 (2H, d, J=9 Hz),7.31 (2H, d, J=9 Hz)

(13) Sodium salt of3-[4-[2-bromo-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine

mp: 188°-190° C.

NMR (DMSO-d₆, δ): 1.27 (3H, t, J=7.5 Hz), 2.82 (2H, q, J=7.5 Hz), 3.63(3H, s), 5.43 (2H, s), 6.94 (1H, s), 7.00 (2H, d, J=9 Hz), 7.20 (1H, s),7.31 (2H, d, J=9 Hz)

(14) Sodium salt of3-[4-[2-bromo-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 171°-173° C.

NMR (DMSO-d₆, δ): 0.93 (3H, t, J=7.5 Hz), 1.62-1.84 (2H, m), 2.78 (2H,t, J=7.5 Hz), 3.63 (3H, s), 5.43 (2H, s), 6.94 (1H, s), 6.99 (2H, d, J=9Hz), 7.19 (1H, s), 7.30 (2H, d, J=9 Hz)

EXAMPLE 43

The following compounds were obtained according to similar manners tothose of Examples 28 and 29 successively.

(1)3-[4-[4-Chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 225°-227° C.

NMR (DMSO-d₆, δ): 0.95 (3H, t, J=7.5 Hz), 1.62-1.86 (2H, m), 2.57 (3H,s), 2.84 (2H, t, J=7.5 Hz), 5.58 (2H, s), 6.92 (1H, d, J=1 Hz), 7.10(1H, d, J=5 Hz), 7.14-7.35 (4H, m), 7.49 (1H, d, J=1 Hz), 8.18 (1H, d,J=5 Hz)

(2)7-Methyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 184°-186° C.

NMR (DMSO-d₆, δ): 0.90 (3H, t, J=7.5 Hz), 1.57-1.79 (2H, m), 1.99 (3H,s), 2.57 (3H, s), 2.82 (2H, t, J=7.5 Hz), 5.60 (2H, s), 6.18 (1H, d,J=4.5 Hz), 6.80 (1H, d, J=4.5 Hz), 7.10 (1H, d, J=5.0 Hz), 7.22 (4H, s),8.19 (1H, d, J=5.0 Hz)

Preparation 149

The following compound was obtained according to a similar manner tothat of Preparation 9.

3-[4-(2-Chloro-4-cyano-1-methyl-3-pyrrolyl)benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 150°-152° C.

NMR (CDCl₃, δ): 0.99 (3H, t, J=7.5 Hz), 1.66-1.90 (2H, m), 2.61 (3H, s),2.65 (3H, s), 2.80 (2H, m), 3.67 (3H, s), 5.50 (2H, s), 6.92 (1H, s),7.11-7.23 (3H, m), 7.50 (2H, d, J=9 Hz)

EXAMPLE 44

The following compound was obtained according to a similar manner tothat of Example 1.

3-[4-[2-Chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

mp: 147°-150° C.

NMR (DMSO-d₆, δ): 0.91 (3H, t, J=7.5 Hz), 1.60-1.81 (2H, m), 2.51 (6H,s), 2.77 (2H, t, J=7.5 Hz), 3.70 (3H, s), 5.48 (2H, s), 6.96 (1H, s),7.10 (2H, d, J=9 Hz), 7.21 (2H, d, J=9 Hz), 7.51 (1H, s)

EXAMPLE 45

The following compound was obtained according to a similar manner tothat of Example 3.

Sodium salt of3-[4-[2-chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine

NMR (D₂ O, δ): 0.68 (3H, t, J=7.5 Hz), 1.32-1.55 (2H, m), 2.29 (3H, s),2.35 (3H, s), 2.58 (2H, t, J=7.5 Hz), 3.31 (3H, s), 5.28 (2H, s), 6.63(1H, s), 6.77-6.90 (4H, m), 7.04 (1H, s)

What we claim is:
 1. A compound of the formula: ##STR32## wherein R¹ ishydrogen, halogen, nitro, lower alkyl, lower alkoxy, amino or acylamino,lower alkoxy, amino or acylamino,R², R³ and R⁴ are each hydrogen,halogen, nitro, cyano, lower alkyl, lower alkenyl, lower alkylthio, monoor di or trihalo(lower)alkyl, oxo(lower)alkyl, hydroxy(lower)alkyl, oroptionally esterified carboxy; or R² and R³ are linked together to form1,3-butadienylene, R⁵ is hydrogen or an imino-protective group, A islower alkylene, Q is CH or N, X is N or CH, Y is NH, O or S, and##STR33## is imidazolyl which is condensed at the 4,5-positions with aheterocyclic ring, which may have substituents selected from the groupconsisting of lower alkyl, halogen, lower alkoxy, hydroxy(lower)alkyland optionally esterified carboxy,provided that Y=NH when X=CH, and apharmaceutically acceptable salt thereof.
 2. A compound of claim 1,wherein ##STR34## is 1H-imidazol-1-yl is condensed with pyrrole,imidazole, pyrazole, pyridine, pyrimidine, furan or thiophene, which mayhave lower alkyl, halogen, lower alkoxy, hydroxy(lower)alkyl, carboxy orlower alkoxycarbonyl substituents.
 3. A compound of claim 2, whereinR¹is hydrogen, halogen, nitro, lower alkyl, lower alkoxy, amino or loweralkanoylamino, R², R³ and R⁴ are each hydrogen, halogen, nitro cyano,lower alkyl, lower alkenyl, lower alkylthio, mono- or di- ortrihalo(lower)alkyl, oxo(lower)alkyl, hydroxy(lower)alkyl, carboxy orlower alkoxycarbonyl, R⁵ is hydrogen or mono- or di- ortriphenyl(lower)alkyl, and ##STR35## is 3H-imidazo[4,5-b]pyridin-3-yl,3H-imidazo[4,5-d]pyramidin-3-yl, 1H-theino[3,4-d]imidazol-1-yl, each ofwhich may have lower alkyl, halogen, lower alkoxy, hydroxy(lower)alkylor lower alkoxycarbonyl substituents.
 4. A compound of claim 3,whereinR¹ and R⁴ are each hydrogen, Q and X are each CH and Y is NH. 5.A compound of claim 6, which is represented by the formula: ##STR36## 6.A compound of claim 5, wherein ##STR37## is 2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl,2,7-di(lower)alkyl-3H-imidazo[4,5-b]pyridin-3-yl,2,5,7-tri(lower)alkyl-3H-imidazo[4,5-b]pyridin3-yl, 5-halo-2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl, 5-lower alkoxy-2-loweralkyl-3H-imidazo[4,5-b]pyridin-3-yl, 2-loweralkyl-3H-imidazo[4,5-d]pyridin-3-yl, 2-loweralkyl-1H-thieno[3,4-d]imidazol-1-yl, and ##STR38## is a group of theformula: ##STR39## wherein R_(a) ² is hydrogen, halogen, cyano, loweralkyl or lower alkylthio, and R_(a) ³ is hydrogen, halogen, nitro, loweralkyl, lower alkenyl, trihalo(lower)alkyl, oxo(lower)alkyl,hydroxy(lower)alkyl or lower alkoxycarbonyl; ##STR40## wherein R_(b) ²and R_(b) ³ are each halogen; ##STR41## wherein R_(c) ² is hydrogen,halogen or lower alkyl, R₃ ³ is lower alkyl, and R_(c) ⁴ is hydrogen orhalogen; ##STR42## wherein R_(d) ² is hydrogen, halogen or lower alkyl,and R_(d) ³ is lower alkyl.
 7. A compound of claim 6, which is selectedfrom the group consisting of:(1)3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]-benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine,(2)2-butyl-3-[4-[3,4-dichloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzoyl]-7-methyl-3H-imidazo[4,5-b]pyridine,(3)3-[4-[2-bromo-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-butyl-7-methyl-3H-imidazo[4,5-b]pyridine,(4)3-[4-[4-bromo-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine,(5)2-butyl-3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-3H-imidazo[4,5-b]pyridine,(6)3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine,(7)7-methyl-3-[4-[4-methyl-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine,(8)7-methyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine,(9)3-[4-[3-chloro-2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine,(10)3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine,(11)5,7-dimethyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine,(12)3-[4-[2,3-dimethyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine,(13)3-[4-[2-chloro-3-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine,(14)2-ethyl-5,7-dimethyl-3-[4-[2-methyl-5-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-3H-imidazo[4,5-b]pyridine,(15)3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]-benzyl]-2-ethyl-7-methyl-3H-imidazo[4,5-b]pyridine,(16)3-[4-[4-chloro-2-(1H-tetrazol-5-yl)-1-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine(17)3-[4-[2-chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine(18)3-[4-[5-bromo-1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]-pyridine(19)3-[4-[1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine,(20)3-[4-[2-chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine,(21)5,7-dimethyl-2-ethyl-3-[4-[1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]imidazo[4,5-b]pyridine,(22)5,7-dimethyl-3-[4-[1-ethyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-propyl-3H-imidazo[4,5-b]pyridine,and (23)3-[4-[2-chloro-1-methyl-4-(1H-tetrazol-5-yl)-3-pyrrolyl]benzyl]-5,7-dimethyl-2-propyl-3H-imidazo[4,5-b]pyridine,ortheir sodium salt or hydrochloride.
 8. A pharmaceutical compositioncomprising a compound of claim 1 or pharmaceutically acceptable saltthereof in association with a pharmaceutically acceptable, substantiallynon-toxic carrier or excipient.
 9. A method for treating or preventingangiotensin II mediated diseases, which comprises administering acompound of claim 1 or pharmaceutically acceptable salt thereof to humanbeing or animals.
 10. A method for treating or preventing hypertensionor heart failure, which comprises administering a compound of claim 1 orpharmaceutically acceptable salt thereof to human being or animals.